Systems, methods, and kits for diagnostics and treatment of viral respiratory infection

ABSTRACT

Systems, methods, and kits for treating, preventing, and diagnosing viral infection using an androgen mediated pathway are described. Additionally, methods and kits for guiding treatment of viral respiratory disease are described by a method for testing for polymorphisms in the androgen receptor gene. Further, systems and methods for treatment of viral respiratory disease with various anti-androgens is detailed. Finally, systems, methods, and kits for treating, preventing, and diagnosing SARS-CoV-2 (COVID-19) are presented.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is related to and claims the benefit of U.S.Provisional Application No. 63/001,629, titled Systems, Methods and Kitsfor Diagnostics and Treatment of SARS-CoV-2, filed on Mar. 30, 2020,U.S. Provisional Application No. 63/004,171, titled Systems, Methods andKits for Diagnostics and Treatment of Viral Respiratory Infection, filedon Apr. 2, 2020, U.S. Provisional Application No. 63/004,398, titledSystems, Methods and Kits for Diagnostics and Treatment of ViralRespiratory Infection, filed on Apr. 2, 2020, U.S. ProvisionalApplication No. 62/704,126, titled Systems, Methods and Kits forDiagnostics and Treatment of Viral Respiratory Infection, filed on Apr.22, 2020, U.S. Provisional Application No. 62/704,416, titled Systems,Methods and Kits for Diagnostics and Treatment of Viral RespiratoryInfection, filed on May 8, 2020, and U.S. Provisional Application No.62/704,531, titled Systems, Methods and Kits for Diagnostics andTreatment of Viral Respiratory Infection, filed on May 14, 2020, theentire contents of each being incorporated herein by reference.

FIELD

The present invention relates to system, methods, and kits for treating,preventing, and diagnosing viral infection using an androgen mediatedpathway. The present invention relates to methods and kits forpredicting viral respiratory disease severity. Additionally, the presentinvention relates to methods and kits for guiding treatment of viralrespiratory disease by testing for polymorphisms in the androgenreceptor gene or genes under regulatory control of the androgenreceptor. Similarly, the following invention relates to systems andmethods for treatment of viral respiratory disease with variousanti-androgens including, but not limited to, androgen receptorantagonists, androgen synthesis inhibitors, or antigonadotropins.Additionally, the present systems, methods, and kits are useful fortreating, preventing, and diagnosing coronavirus, e.g., SARS-CoV-2(COVID-19).

BACKGROUND

In late 2019, a novel coronavirus, subsequently named SARS-CoV-2(COVID-19), was first reported in Hubei province in China. Since it wasfirst reported, a worldwide pandemic has ensued affecting more than450,000 individuals as of March 2020. In the midst of the pandemic,epidemiological reports unveiled a disproportionate low rate of severecases among adult females compared to adult males, 42% and 58%,respectively. Similarly, the rate of severe cases among pre-pubescentchildren was exceptionally low at 0.6% (See Guan W J, Ni Z Y, Hu Y,Liang W H, Ou C Q, et al. Clinical Characteristics of CoronavirusDisease 2019 in China. N Engl J Med. 2020). An explanation for theskewed prevalence of severe COVID-19 infection in adult males has yet tobe elucidated.

In newborns, it has long been recognized that male infants are moresusceptible to respiratory distress syndrome (See Torday J S, Nielsen HC, Fend Mde M, Avery M E. Sex differences in fetal lung maturation. AmRev Respir Dis. 1981; 123(2): 205-208) and less likely to respond toprenatal glucocorticoid therapy to protect against respiratory distress.Respiratory distress is intimately tied to the production of pulmonarysurfactant, e.g., pulmonary surfactant proteins have been demonstratedto protect against influenza A (See Hartshorn K L, Crouch E C, White MR, Eggleton P, Tauber A I, Chang D, Sastry K. Evidence for a ProtectiveRole of Pulmonary Surfactant Protein D (SP-D) Against Influenza AViruses. J Clin Invest. 1994; 94 (1): 311-319). In animal studies, itwas demonstrated that a sexual dimorphism in fetal pulmonary surfactantproduction is influenced by the androgen receptor (AR) (See Nielsen H C.Androgen receptors influence the production of pulmonary surfactant inthe testicular feminization mouse fetus. J Clin Invest. 1985; 76(1):177-181). For example, in rabbits, dihydrotestosterone was shown toinhibit fetal pulmonary surfactant production in both males and femaleswhile an anti-androgen, flutamide, was demonstrated to remove the sexualdimorphism in surfactant production.

While severe COVID-19 symptoms are primarily manifested in older adults,the similar sexual dimorphism in the severity of respiratory disease isof interest. In addition, AR expression is low prior to pubertalmaturation and may contribute to the low incidence of severe COVID-19infection in children. The lower rate of severe COVID-19 infection infemale patients may be attributed to lower androgen receptor expression.

SUMMARY

Systems, methods, and kits are disclosed herein for diagnosing andtreating viral respiratory infection by first measuring polymorphisms inthe androgen receptor gene or polymorphisms in genes under regulatorycontrol of the androgen receptor. Identification of polymorphisms in theandrogen receptor gene can be used to guide treatments of viralrespiratory disease. Treatments for viral respiratory disease mayinclude, but are not limited to, androgen receptor antagonists, androgensynthesis inhibitors, or antigonadotropins. Specifically, the presentsystems, methods, and kits are useful for treating, preventing, anddiagnosing viral respiratory disease as a result of coronavirusinfection, e.g., SARS-CoV-2 (COVID-19).

In an exemplary embodiment, a composition administered to a subjecthaving or suspected of having a viral respiratory infection includes anyone or combination of: an androgen receptor antagonists oranti-androgen; an androgen synthesis inhibitor; an agent that countersthe effect of androgens; a globulin (SHBG) stimulator; anantigonadotropin; a mineralocorticoid to suppress androgen production inthe adrenal gland; a glucocorticoid to suppress androgen production inthe adrenal gland; an insulin sensitizing medication; and a vaccine oran immunogen against androstenedione that reduces the level oftestosterone or increases estrogen.

In some embodiments: the anti-androgen is any one or combination of:cyproterone acetate, megestrol acetate, chlormadinone acetate,spironolactone, medrogestone, oxendolone, osaterone, bifluranol acetate,finasteride, dutastride, flutamide, bicalutamide, nilutamide,topilutamide, enzalutamide, apalutamide, dienogest, drospirenone,medrogestone, nomegestrol acetate, promegestone, trimegestone,ketoconazole, abiraterone acetate, seviteronel, aminoglutethimide,epristeride, alfaestradiol, isotretinoin, saw palmetto, marijuana,cannabinoids, darolutamide, EZN-4176, AZD-3514, and AZD-5312, apatorsen,galeterone, ODM-2014, TRC-253, BMS-641988, proxalutamid, Luteinizinghormone-releasing hormone (LH-RH), follicle-stimulating hormone (FSH),triptorelin pamoate, docetaxel, diethylstilbestrol, tadalafil,silodosin, tamsulosin hydrochloride, naftopidil, solifenacin succinate,tamsulosin, tamsulosin hydrochloride, alfuzosin hydrochloride, prazosinhydrochloride, doxazosin, doxazosin mesylate, solifenacin succinate,allylestrenol, benzydamine hydrochloride, cefatrizine, chlormadinoneacetate, flavoxate hydrochloride, gestonorone caproate, indoraminhydrochloride, mepartricin, oxybutynin chloride, phenoxybenzaminehydrochloride, terazosin, terazosin hydrochloride, or degarelix. Theagent that counters the effect of androgens is a sex hormone-bindingglobulin (SHBG) stimulator. The glucocorticoid is anticorticotropin. Theinsulin sensitizing medication is metformin.

In some embodiments, the composition is formulated to facilitateadministration of the composition topically to the skin, nasally,sub-lingually, orally, by injection (e.g., intramuscular, intravenous,subcutaneous, depot), via inhalation, or ocular application.

In some embodiments, the viral respiratory infection is any one orcombination of coronavirus, influenza, influenza A, influenza B,SARS-CoV-1, SARS-CoV-2, MERS-CoV, or rhinoviruses.

In some embodiments, the compositions is formulated to alter androgenreceptor function and subsequently down stream genes under regulatorycontrol of the androgen receptor.

In some embodiments, the down stream genes include any one orcombination of angiotensin converting enzyme 2 (ACE2), furin, andtransmembrane protease serine 2 (TMPRSS2).

In some embodiments, the composition is formulated to block theproduction of proteins in the lung so as to alter viral entry into cellsor to bolster host immunity.

In some embodiments, the anti-androgen is combined with any one orcombination of an anti-inflammatory agent, an anti-bacterial agent, oraspartame.

In some embodiments, the composition is formulated for use as atreatment of the viral respiratory infection, a therapy for the viralrespiratory infection, a prophylactic for the viral respiratoryinfection, a preventive measure for contracting the viral respiratoryinfection, a diagnosis of a type of viral respiratory infection, aprediction for respiratory disease severity of the viral respiratoryinfection, a prediction for determining an effective treatment orprophylactic composition, and/or a prediction for determining aneffective administration dosage of the composition for use as atreatment or prophylactic.

In an exemplary embodiment, a method of using a composition on a subjecthaving or suspected of having a viral respiratory infection involvesadministering a composition to a subject, the composition including anyone or combination of: an androgen receptor antagonists oranti-androgen; an androgen synthesis inhibitor; an agent that countersthe effect of androgens; a globulin (SHBG) stimulator; anantigonadotropin; a mineralocorticoid to suppress androgen production inthe adrenal gland; a glucocorticoid to suppress androgen production inthe adrenal gland; an insulin sensitizing medication; and vaccine or animmunogen against androstenedione that reduces the level of testosteroneor increases estrogen.

In some embodiments: the anti-androgen is any one or combination of:cyproterone acetate, megestrol acetate, chlormadinone acetate,spironolactone, medrogestone, oxendolone, osaterone, bifluranol acetate,finasteride, dutastride, flutamide, bicalutamide, nilutamide,topilutamide, enzalutamide, apalutamide, dienogest, drospirenone,medrogestone, nomegestrol acetate, promegestone, trimegestone,ketoconazole, abiraterone acetate, seviteronel, aminoglutethimide,epristeride, alfaestradiol, isotretinoin, saw palmetto, marijuana,cannabinoids, darolutamide, EZN-4176, AZD-3514, and AZD-5312, apatorsen,galeterone, ODM-2014, TRC-253, BMS-641988, proxalutamid, Luteinizinghormone-releasing hormone (LH-RH), follicle-stimulating hormone (FSH),triptorelin pamoate, docetaxel, diethylstilbestrol, tadalafil,silodosin, tamsulosin hydrochloride, naftopidil, solifenacin succinate,tamsulosin, tamsulosin hydrochloride, alfuzosin hydrochloride, prazosinhydrochloride, doxazosin, doxazosin mesylate, solifenacin succinate,allylestrenol, benzydamine hydrochloride, cefatrizine, chlormadinoneacetate, flavoxate hydrochloride, gestonorone caproate, indoraminhydrochloride, mepartricin, oxybutynin chloride, phenoxybenzaminehydrochloride, terazosin, terazosin hydrochloride, or degarelix. Theagent that counters the effect of androgens is a sex hormone-bindingglobulin (SHBG) stimulator. The glucocorticoid is anticorticotropin. Theinsulin sensitizing medication is metformin.

In some embodiments, the administration of the composition involves anyone or combination of topical application to the skin, nasalapplication, oral application, via injection, via inhalation, or ocularapplication.

In some embodiments, the viral respiratory infection is any one orcombination of coronavirus, influenza, influenza A, influenza B,SARS-CoV-1, SARS-CoV-2, MERS-CoV or rhinoviruses.

In some embodiments, the method involves altering androgen receptorfunction and subsequently down stream genes under regulatory control ofthe androgen receptor.

In some embodiments, the down stream genes include any one orcombination of angiotensin converting enzyme 2 (ACE2), furin, andtransmembrane protease serine 2 (TMPRSS2).

In some embodiments, the method involves blocking the production ofproteins in the lung so as to alter viral entry into cells or to bolsterhost immunity.

In some embodiments, the composition is use as a treatment of the viralrespiratory infection, a therapy for the viral respiratory infection, aprophylactic for the viral respiratory infection, a preventive measurefor contracting the viral respiratory infection, a diagnosis of a typeof viral respiratory infection, a prediction for respiratory diseaseseverity of the viral respiratory infection, a prediction fordetermining an effective treatment or prophylactic composition, and/or aprediction for determining an effective administration dosage of thecomposition for use as a treatment or prophylactic.

In some embodiments, the treatment involves administering thecomposition as a treatment for the viral respiratory infection and/or aprophylactic for the viral respiratory infection before, during, and/orafter the subject is first diagnosed with the viral respiratoryinfection and/or before, during, and/or after the subject ishospitalized due to the viral respiratory infection.

In some embodiments, the method involves predicting anti-androgentreatment response via evaluation of a genetic variation of the androgenreceptor (AR) gene.

In some embodiments, the method involves guiding selection ofanti-androgen treatment and/or dosage selection of the selectedanti-androgen treatment based on the predicted anti-androgen treatmentresponse.

In some embodiments, the method involves predicting the anti-androgentreatment response involves measuring polymorphisms in the AR gene.

In some embodiments, the method involves predicting infection symptomseverity, infection mortality, and/or whether the subject will need aventilator or respiration due to the infection.

In some embodiments: the number of cytosine-adenine-guanine (CAG)repeats in the first exon of the AR gene, the number ofguanine-guanine-(any nucleotide) (GGN) repeats in the first exon in theAR gene, and/or a ratio of CAG/GGN repeats is used as the geneticvariant; and a cut off value for the number of CAG repeats the firstexon of AR gene is used to define a person with androgen sensitivity.

In some embodiments, the cut-off value for the number of CAG repeats thefirst exon of AR gene is between 10 and 30.

In some embodiments, variants in the promoter region of the AR are usedas the genetic variant.

In some embodiments, the method involves administering the compositionroutinely.

In some embodiments, the anti-androgen is combined with any one orcombination of an anti-inflammatory agent, an anti-bacterial agent, oraspartame.

In an exemplary embodiment, a kit includes a deoxyribonucleic acid (DNA)sample collection unit configured to obtain a genetic sample via buccalswab, saliva sample, blood sample, tissue sample, and/or hair sample; aviral respiratory infection sensitivity unit configured to identifypolymorphisms in the androgen receptor gene; and a DNA diagnostic assay.

In an exemplary embodiment, a method of identifying whether a person isat risk of mortality or developing severity of infection following viralrespiratory infection involves determining the risk of severity ormortality of the viral respiratory infection by identifying andmeasuring promotor regions in any one or combination of the androgenreceptor (AR) gene, the TMPRSS2 gene, the furin gene, or the ACE2 gene.

In some embodiments, the method involves predicting anti-androgentreatment response via evaluation of a genetic variation of the AR gene,the TMPRSS2 gene, the furin gene, or the ACE2 gene.

In some embodiments, the genetic variation includes any one orcombination of: one or more of: F877L/T878A, F877L, T878A, rs137852591,rs104894742, rs1057518177, rs1057521121, rs1057521122, rs1057523747,rs1064793480, rs1064793645, rs1064794065, rs1064794069, rs1064795250,rs1085307685, rs1085307962, rs12014709, rs1204038, rs1337080,rs137852562, rs137852563, rs137852564, rs137852565, rs137852566,rs137852567, rs137852568, rs137852569, rs137852570, rs137852571,rs137852572, rs137852573, rs137852574, rs137852575, rs137852576,rs137852577, rs137852578, rs137852579, rs137852580, rs137852581,rs137852582, rs137852583, rs137852584, rs137852585, rs137852586,rs137852587, rs137852588, rs137852589, rs137852590, rs137852592,rs137852593, rs137852594, rs137852595, rs137852596, rs137852597,rs137852598, rs137852599, rs137852600, rs137852601, rs1800053,rs201934623, rs2361634, rs5031002, rs5918757, rs6152, rs6624304,rs750324117, rs754201976, rs755226547, rs759327087, rs864622007,rs869320731, rs869320732, rs878853033, rs886039558, rs886041050,rs886041128, rs886041129, rs886041130, rs886041131, rs886041132,rs886041133, rs886041352, rs9332969, or rs9332971; one or more of:rs12329760, rs2070788, rs383510, rs463727, rs34624090, rs55964536,rs734056, rs4290734, rs34783969, rs11702475, rs35899679, rs35041537,rs8134378, rs2070788, rs9974589, rs7364083, or rs2070788; one or moreof: rs2285666, G8790A, rs35803318, rs1978124, rs2048683, rs2074192,rs2106809, rs2285666, rs233575, rs4240157, rs4646155, rs4646156,rs4646174, rs4646176, rs4646188, rs6632677, rs714205, or rs879922; orone or more of: rs17514846, rs2071410, rs4702, rs4932178, rs6226, orrs6227.

In an exemplary embodiment, a composition administered to a subjecthaving or suspected of having a viral respiratory infection includescomprising dutasteride, wherein the composition is formulated for use asa treatment of the viral respiratory infection, a therapy for the viralrespiratory infection, a prophylactic for the viral respiratoryinfection, a preventive measure for contracting the viral respiratoryinfection, a diagnosis of a type of viral respiratory infection, aprediction for respiratory disease severity of the viral respiratoryinfection, a prediction for determining an effective treatment orprophylactic composition, and/or a prediction for determining aneffective administration dosage of the composition for use as atreatment or prophylactic.

In an exemplary embodiment, a method of using a composition on a subjecthaving or suspected of having a viral respiratory infection involvesadministering a composition to the subject, the composition includingdutasteride, wherein the composition is use as a treatment of the viralrespiratory infection, a therapy for the viral respiratory infection, aprophylactic for the viral respiratory infection, a preventive measurefor contracting the viral respiratory infection, a diagnosis of a typeof viral respiratory infection, a prediction for respiratory diseaseseverity of the viral respiratory infection, a prediction fordetermining an effective treatment or prophylactic composition, and/or aprediction for determining an effective administration dosage of thecomposition for use as a treatment or prophylactic.

In some embodiments, the composition is administered orally.

In some embodiments, the composition is administered so that thedutasteride is present in a range from 0.1 mg/day to 1.0 mg/day.

In some embodiments, the method involves administering the compositionat any time before the subject is exposed to the viral respiratoryinfection.

In some embodiments, the composition is administered at any time withina time frame of thirty days prior to the patient being exposed to theviral respiratory infection.

In an exemplary embodiment, a method of using a composition on a subjecthaving or suspected of having a viral respiratory infection involves:administering, via inhalation or injection, a small-interfering RNA(siRNA) directed against any one or combination of an androgen receptor(AR), TMPRSS2, and ACE2; wherein the viral respiratory infectionincludes any one or combination of coronavirus, influenza, influenza A,influenza B, SARS-CoV-1, SARS-CoV-2, MERS-CoV, or rhinoviruses.

In an exemplary embodiment, a composition for treatment of a viralrespiratory infection includes any one or combination of: an androgenreceptor antagonists or anti-androgen; an androgen synthesis inhibitor;an agent that counters the effect of androgens; a globulin (SHBG)stimulator; an antigonadotropin; a mineralocorticoid to suppressandrogen production in the adrenal gland; a glucocorticoid to suppressandrogen production in the adrenal gland; an insulin sensitizingmedication; and a vaccine or an immunogen against androstenedione thatreduces the level of testosterone or increases estrogen.

In some embodiments, the anti-androgen is any one or combination of:cyproterone acetate, megestrol acetate, chlormadinone acetate,spironolactone, medrogestone, oxendolone, osaterone, bifluranol acetate,finasteride, dutastride, flutamide, bicalutamide, nilutamide,topilutamide, enzalutamide, apalutamide, dienogest, drospirenone,medrogestone, nomegestrol acetate, promegestone, trimegestone,ketoconazole, abiraterone acetate, seviteronel, aminoglutethimide,epristeride, alfaestradiol, isotretinoin, saw palmetto, marijuana,cannabinoids, darolutamide, EZN-4176, AZD-3514, and AZD-5312, apatorsen,galeterone, ODM-2014, TRC-253, BMS-641988, proxalutamid, Luteinizinghormone-releasing hormone (LH-RH), follicle-stimulating hormone (FSH),triptorelin pamoate, docetaxel, diethylstilbestrol, tadalafil,silodosin, tamsulosin hydrochloride, naftopidil, solifenacin succinate,tamsulosin, tamsulosin hydrochloride, alfuzosin hydrochloride, prazosinhydrochloride, doxazosin, doxazosin mesylate, solifenacin succinate,allylestrenol, benzydamine hydrochloride, cefatrizine, chlormadinoneacetate, flavoxate hydrochloride, gestonorone caproate, indoraminhydrochloride, mepartricin, oxybutynin chloride, phenoxybenzaminehydrochloride, terazosin, terazosin hydrochloride, or degarelix. Theagent that counters the effect of androgens is a sex hormone-bindingglobulin (SHBG) stimulator. The glucocorticoid is anticorticotropin. Theinsulin sensitizing medication is metformin.

In some embodiments, the composition is formulated to facilitateadministration of the composition topically to the skin, nasally,sub-lingually orally, by injection, via inhalation, or ocularapplication.

In some embodiments the viral respiratory infection is any one orcombination of coronavirus, influenza, influenza A, influenza B,SARS-CoV-1, SARS-CoV-2, MERS-CoV, or rhinoviruses.

In some embodiments the anti-androgen is combined with any one orcombination of an anti-inflammatory agent, an anti-bacterial agent, oraspartame.

In some embodiments the composition is formulated for use as a treatmentof the viral respiratory infection, a therapy for the viral respiratoryinfection, a prophylactic for the viral respiratory infection, and/or apreventive measure for contracting the viral respiratory infection.

In some embodiments the composition is further formulated for use as atreatment for prostate cancer, castration-resistant prostate cancer,metastatic castration-sensitive prostate cancer, non-metastaticcastration-resistant prostate cancer and/or benign prostatichyperplasia.

In an exemplary embodiment, a method of treating a patient having orsuspected of having a viral respiratory infection involves administeringa composition to the patient, the composition including any one orcombination of: an androgen receptor antagonists or anti-androgen; anandrogen synthesis inhibitor; an agent that counters the effect ofandrogens; a globulin (SHBG) stimulator; an antigonadotropin; amineralocorticoid to suppress androgen production in the adrenal gland;a glucocorticoid to suppress androgen production in the adrenal gland;an insulin sensitizing medication; and vaccine or an immunogen againstandrostenedione that reduces the level of testosterone or increasesestrogen.

In some embodiments, the anti-androgen is any one or combination of:cyproterone acetate, megestrol acetate, chlormadinone acetate,spironolactone, medrogestone, oxendolone, osaterone, bifluranol acetate,finasteride, dutastride, flutamide, bicalutamide, nilutamide,topilutamide, enzalutamide, apalutamide, dienogest, drospirenone,medrogestone, nomegestrol acetate, promegestone, trimegestone,ketoconazole, abiraterone acetate, seviteronel, aminoglutethimide,epristeride, alfaestradiol, isotretinoin, saw palmetto, marijuana,cannabinoids, darolutamide, EZN-4176, AZD-3514, and AZD-5312, apatorsen,galeterone, ODM-2014, TRC-253, BMS-641988, proxalutamid, Luteinizinghormone-releasing hormone (LH-RH), follicle-stimulating hormone (FSH),triptorelin pamoate, docetaxel, diethylstilbestrol, tadalafil,silodosin, tamsulosin hydrochloride, naftopidil, solifenacin succinate,tamsulosin, tamsulosin hydrochloride, alfuzosin hydrochloride, prazosinhydrochloride, doxazosin, doxazosin mesylate, solifenacin succinate,allylestrenol, benzydamine hydrochloride, cefatrizine, chlormadinoneacetate, flavoxate hydrochloride, gestonorone caproate, indoraminhydrochloride, mepartricin, oxybutynin chloride, phenoxybenzaminehydrochloride, terazosin, terazosin hydrochloride, or degarelix. Theagent that counters the effect of androgens is a sex hormone-bindingglobulin (SHBG) stimulator. The glucocorticoid is anticorticotropin. Theinsulin sensitizing medication is metformin.

In some embodiments, the administration of the composition involves anyone or combination of topical application to the skin, nasalapplication, sub-lingual application, oral application, via injection,via inhalation, or ocular application.

In some embodiments, the viral respiratory infection is any one orcombination of coronavirus, influenza, influenza A, influenza B,SARS-CoV-1, SARS-CoV-2, MERS-CoV or rhinoviruses.

In some embodiments, the composition is used as a treatment for theviral respiratory infection, a therapy for the viral respiratoryinfection, a prophylactic for the viral respiratory infection, and/or apreventive measure for contracting the viral respiratory infection.

In some embodiments, the treatment involves administering thecomposition as a treatment for the viral respiratory infection and/or aprophylactic for the viral respiratory infection before, during, and/orafter the patient is first diagnosed with the viral respiratoryinfection and/or before, during, and/or after the patient ishospitalized due to the viral respiratory infection.

In some embodiments, the composition is further used as a treatment forprostate cancer, castration-resistant prostate cancer, metastaticcastration-sensitive prostate cancer, non-metastaticcastration-resistant prostate cancer and/or benign prostatichyperplasia.

In some embodiments, the method further involves predictinganti-androgen treatment response via evaluation of genetic variation inthe gene and/or promotor region of the androgen receptor (AR).

In some embodiments, the method further involves guiding selection ofanti-androgen treatment and/or dosage selection of the selectedanti-androgen treatment based on the predicted anti-androgen treatmentresponse.

In some embodiments, predicting the anti-androgen treatment responseinvolves measuring polymorphisms in the AR gene.

In some embodiments, the number of cytosine-adenine-guanine (CAG)repeats in the first exon of the AR gene, the number ofguanine-guanine-(any nucleotide) (GGN) repeats in the first exon in theAR gene, and/or a ratio of CAG/GGN repeats is used as the geneticvariant. A cut off value for the number of CAG repeats the first exon ofAR gene is used to define a person with androgen sensitivity.

In some embodiments, the cut-off value for the number of CAG repeats thefirst exon of AR gene is between 10 and 30.

In some embodiments, variants in the promoter region of the AR are usedas the genetic variant.

In some embodiments, the anti-androgen is combined with any one orcombination of an anti-inflammatory agent, an anti-bacterial agent, oraspartame.

In some embodiments, the viral respiratory infection is SARS-CoV-2.

In some embodiments, administering the composition involvesadministering topical skin application of finasteride at 1-30% (w/w),oral finasteride at 0.01-30 mg, dutasteride at 0.1 mg/day to 3.0 mg/day,degarelix at 24 mg-720 mg, oral cannabidiol at 1-30/mg/Kg/day, oralflutamide at 75-2,250 mg/day, enzalutamide at 16-480 mg qd, oraldutasteride at 0.025-0.75 mg/day, apalutamide at 6-180 mg 4 times perday, injection of 30-900 mg of cyproterone acetate, subcutaneousinjection of 12-360 mg of degarelix, bicalutamide at 5-150 mg per day,subcutaneous injection of 12-360 mg of degarelix, oral darolutamide at30-900 mg twice daily, abiraterone at 50-1500 mg twice daily, oralnilutamide at 30-900 mg once daily, or docetaxel at 7.5-225 mg/m2 IVover 1 hour.

In some embodiments, administering the composition involvesadministering topical skin application of finasteride at 1-10% (w/w),oral finasteride at 0.1-10 mg, dutasteride at 0.1 mg/day to 1.0 mg/day,degarelix at 24 mg-240 mg, oral cannabidiol at 1-10/mg/Kg/day, oralflutamide at 75-750 mg/day, enzalutamide at 16-160 mg qd, oraldutasteride at 0.025-0.25 mg/day, apalutamide at 6-60 mg 4 times perday, injection of 30-300 mg of cyproterone acetate, subcutaneousinjection of 12-120 mg of degarelix, bicalutamide at 5-50 mg per day,subcutaneous injection of 12-120 mg of degarelix, oral darolutamide at30-300 mg twice daily, abiraterone at 50-500 mg twice daily, oralnilutamide at 30-300 mg once daily, or docetaxel at 7.5-750 mg/m2 IVover 1 hour.

In an exemplary embodiment, a method of treating a patient having orsuspected of having a viral respiratory infection involves: determiningthe risk of severity or mortality of the viral respiratory infection forthe patient by identifying and measuring genetic variation in the geneand/or promotor region of any one or combination of the androgenreceptor (AR), TMPRSS2, furin, or ACE2; selecting a composition and adosage for the composition based on the determined risk of severity ormortality; and administering the composition to the patient, thecomposition including any one or combination of: an androgen receptorantagonists or anti-androgen; an androgen synthesis inhibitor; an agentthat counters the effect of androgens; a globulin (SHBG) stimulator; anantigonadotropin; a mineralocorticoid to suppress androgen production inthe adrenal gland; a glucocorticoid to suppress androgen production inthe adrenal gland; an insulin sensitizing medication; and vaccine or animmunogen against androstenedione that reduces the level of testosteroneor increases estrogen.

In some embodiments, the method involves use of a kit, wherein: agenetic sample via buccal swab, saliva sample, blood sample, tissuesample, and/or hair sample is obtained via a deoxyribonucleic acid (DNA)sample collection unit; polymorphisms in the androgen receptor gene areidentified via a viral respiratory infection sensitivity unit; and anassay analysis is performed using a DNA diagnostic assay.

In some embodiments, the method further involves predictinganti-androgen treatment response via evaluation of a genetic variationin the gene and/or promotor region in any one or combination of AR,TMPRSS2, furin, or ACE2.

In some embodiments, the genetic variation includes any one orcombination of: one or more of: F877L/T878A, F877L, T878A, rs137852591,rs104894742, rs1057518177, rs1057521121, rs1057521122, rs1057523747,rs1064793480, rs1064793645, rs1064794065, rs1064794069, rs1064795250,rs1085307685, rs1085307962, rs12014709, rs1204038, rs1337080,rs137852562, rs137852563, rs137852564, rs137852565, rs137852566,rs137852567, rs137852568, rs137852569, rs137852570, rs137852571,rs137852572, rs137852573, rs137852574, rs137852575, rs137852576,rs137852577, rs137852578, rs137852579, rs137852580, rs137852581,rs137852582, rs137852583, rs137852584, rs137852585, rs137852586,rs137852587, rs137852588, rs137852589, rs137852590, rs137852592,rs137852593, rs137852594, rs137852595, rs137852596, rs137852597,rs137852598, rs137852599, rs137852600, rs137852601, rs1800053,rs201934623, rs2361634, rs5031002, rs5918757, rs6152, rs6624304,rs750324117, rs754201976, rs755226547, rs759327087, rs864622007,rs869320731, rs869320732, rs878853033, rs886039558, rs886041050,rs886041128, rs886041129, rs886041130, rs886041131, rs886041132,rs886041133, rs886041352, rs9332969, or rs9332971; one or more of:rs12329760, rs2070788, rs383510, rs463727, rs34624090, rs55964536,rs734056, rs4290734, rs34783969, rs11702475, rs35899679, rs35041537,rs8134378, rs2070788, rs9974589, rs7364083, or rs2070788; one or moreof: rs2285666, G8790A, rs35803318, rs1978124, rs2048683, rs2074192,rs2106809, rs2285666, rs233575, rs4240157, rs4646155, rs4646156,rs4646174, rs4646176, rs4646188, rs6632677, rs714205, or rs879922; orone or more of: rs17514846, rs2071410, rs4702, rs4932178, rs6226, orrs6227.

DETAILED DESCRIPTION

SARS-CoV-2 is part of the coronavirus family of viruses includingSARS-CoV-1 and MERS-CoV. Coronavirus predominantly infects type IIpneumocytes in the human lung (See Shieh W J, Hsiao C H, Paddock C D,Guarner J, Goldsmith C S, et al. Immunohistochemical, in situhybridization, and ultrastructural localization of SARS-associatedcoronavirus in lung of a fatal case of severe acute respiratory syndromein Taiwan. Hum Pathol. 2005; 36(3): 303-309). It has been demonstratedthat SARS-CoV-2 cell entry depends on priming of a viral spike surfaceprotein by transmembrane protease serine 2 (TMPRSS2) present in thehost. In type II pneumocytes, TMPRSS2 expression is associated with anincrease in androgen receptor (AR) expression (See Mikkonen L,Pihlajamaa P, Sahu B, Zhang F P, Janne O A. Androgen Receptor andAndrogen-Dependent Gene Expression in Lung. Mol Cell Endocrinol. 2010;317 (1-2): 14-24), specifically connecting AR expression to SARSCoV-2,due to AR-regulated TMPRSS2 gene promoter (See Lin B, Ferguson C, WhiteJ T, Wang S, Vessella R, True L D, et al. Prostate-localized andandrogen-regulated expression of the membrane-bound serine proteaseTMPRSS2. Cancer Res 1999; 59: 4180-4). Moreover, angiotensin convertingenzyme 2 (ACE2) has been recognized as the attachment molecule to theviral spike surface protein, thus termed the “receptor of SARS-CoV-2”(See Y. Qiu, Y.-B. Zhao, Q. Wang, J.-Y. Li, Z.-J. Zhou, C.-H. Liao,X.-Y. Ge, Predicting the angiotensin converting enzyme 2 (ACE2)utilizing capability as the receptor of SARS-CoV-2, Microbes andInfection, https://doi.org/10.1016/j.micinf.2020.03.003).

As used herein, the terms “prevent” or “prevention” and otherderivatives of the words, when used in reference to viral respiratoryinfection, e.g., viral respiratory infection, refer to a reducedlikelihood of viral respiratory infection in an individual receiving agiven treatment relative to that of a similar individual at risk forviral respiratory infection but not receiving that treatment. As such,the terms “prevent” and “prevention” encompass a treatment that resultsin a lesser degree of viral respiratory infection, e.g., viralrespiratory infection, than would be otherwise expected for a givenindividual. Efficacy for prevention of viral respiratory infection,e.g., viral respiratory infection, can be established through controlledstudies, e.g., in which a subject is administered a treatment (e.g., aninhaled treatment) and another subject is administered a placebo. Underthese circumstances, if the subject treated with the inhaled treatmentundergoes less severe viral respiratory infection symptoms over timerelative to the subject receiving the placebo, e.g., at least 5% less,at least 10% less, at least 15% less, at least 20% less, at least 25%less, at least 30% less, at least 35% less, at least 40% less, at least45% less, at least 50% less or beyond, the treatment is effective forthe prevention of viral respiratory infection

As used herein, the terms “treat,” “treatment,” or “treating” refer totherapeutic treatments, wherein the object is to reverse, alleviate,ameliorate, inhibit, slow down or stop the progression or severity of adisease or condition, e.g., viral respiratory infection. The term“treating” includes reducing or alleviating at least one adverse effector symptom of a disease or condition, e.g., viral respiratory infection.Treatment is generally “effective” if one or more symptoms are reduced.Alternatively, treatment is “effective” if the progression of a diseaseis reduced or halted. That is, “treatment” includes not just theimprovement of symptoms, but also a cessation of, or at least slowingof, progress or worsening of symptoms compared to what would be expectedin the absence of treatment. Beneficial or desired clinical resultsinclude, but are not limited to, alleviation of one or more symptom(s),diminishment of extent of disease, stabilized (i.e., not worsening)state of disease, delay or slowing of disease progression, ameliorationor palliation of the disease state, remission (whether partial ortotal), and/or decreased mortality. For example, treatment is consideredeffective if: 1) the risk or propensity of a person having a viralrespiratory infection being hospitalized, being admitted to an intensivecare unit (ICU), or dying as a result is reduced; 2) the rate at which aperson having a viral respiratory infection recovers or stabilizes isincreased; 3) the rate at which a person having a viral respiratoryinfection is discharged from the hospital is increased; 4) the abilityfor a person having a viral respiratory infection to recover orstabilize is improved; 5) the ability to diagnose a person as having aviral respiratory infection is improved; 6) the time to diagnose aperson having a viral respiratory infection is reduced; 7) the abilityto prevent a person from being infected with a viral respiratoryinfection is improved; 8) the ability to predict viral respiratorydisease severity (e.g., is a ventilator or respirator will be needed fortreatment) is increased. The term “treatment” of a disease also includesproviding relief from the symptoms or side-effects of the disease(including palliative treatment). Treatment can involve administering atherapeutically effective amount of any one or combination of thecompositions disclosed herein.

As used herein the term “comprising” or “comprises” is used in referenceto compositions, methods, etc. refers to component(s) or method stepsthat are present in the method or composition, yet allows for thecomposition, method, etc. to also include unspecified elements.

The term “consisting of” refers to compositions, methods, and respectivecomponents thereof as described herein, which are exclusive of anyelement not recited in that description of the embodiment.

As used herein the term “consisting essentially of” refers to thoseelements required for a given embodiment. The term permits the presenceof elements that do not materially affect the basic and novel orfunctional characteristic(s) of that embodiment.

As used herein the term “viral respiratory infection” refers to allforms of human lung disease stemming from a viral infection includingcoronavirus, influenza, influenza A, influenza B, SARS-CoV-1,SARS-CoV-2, MERS-CoV and rhinoviruses. The term permits the presence ofelements that do not materially affect the basic and novel or functionalcharacteristic(s) of that embodiment.

The singular terms “a,” “an,” and “the” include plural referents unlesscontext clearly indicates otherwise. Similarly, the word “or” isintended to include “and” unless the context clearly indicatesotherwise. Although methods and materials similar or equivalent to thosedescribed herein can be used in the practice or testing of thisdisclosure, suitable methods and materials are described below. Theabbreviation, “e.g.” is derived from the Latin exempli gratia, and isused herein to indicate a non-limiting example. Thus, the abbreviation“e.g.” is synonymous with the term “for example.”

Various aspects of the technology describe detecting androgensensitivity in a subject by measuring polymorphisms in the androgenreceptor gene. Androgen Receptor (AR) genetic variation refers to DNAgenetic variations, expression of AR in specific tissue (RNA), includingmethylation analysis of AR (i.e., in the case of X-chromosomeinactivation). Specific details for detecting polymorphisms in theandrogen receptor can be found in literature, e.g., See Androgens andAndrogen Receptor: Mechanisms, Functions, and Clini Applications. UnitedStates, Springer US, 2012, which is incorporated here in its entirety.Polymorphisms in the androgen receptor can be used to infer a subjecthas androgen sensitivity.

Applicants disclose herein systems, methods, and kits for treating,preventing, and diagnosing viral respiratory infection by firstmeasuring polymorphisms in the androgen receptor gene. The methodincludes the use of compositions including any one or combination of thefollowing: androgen receptor antagonists, androgen synthesis inhibitors,agents that counter the effect of androgens such as sex hormone-bindingglobulin (SHBG) stimulators, antigonadotropins, mineralocorticoids andglucocorticoids (anticorticotropins) suppressing androgen production inthe adrenal gland, insulin sensitizing medications (e.g., metformin),and vaccines or immunogens against androstenedione that reduce the levelof testosterone as a treatment for viral respiratory disease. The use ofthe composition can involve administering the composition to a subjector a patient. For instance, the composition can be administeredtopically, nasally, orally, by injection, or be applied topically to thelung, i.e. inhaled. Compositions applied to a subject alter androgenreceptor function and subsequently down stream genes under regulatorycontrol of the androgen receptor. Such genes include but are not limitedto, angiotensin converting enzyme 2 (ACE2), furin, and transmembraneprotease serine 2 (TMPRSS2). Blocking the production of certain proteinsin the lung may be beneficial to altering viral entry into cells orbolstering host immunity. For example, TMPRSS2 priming of a viral spikesurface protein is required for SARS-CoV-2 cell entry; TMPRSS2expression is under control of the androgen receptor. As such, blockingthe expression of the androgen receptor or altering AR activity (e.g.,with and AR antagonist) would decrease the amount of TMPRSS2 expressionand lead to reduced viral entry. Other embodiments are described below.

In certain embodiments, a genetic variation in the androgen receptor(AR) gene can be used to predict mortality from viral respiratoryinfection. In another embodiment, a genetic variation in the androgenreceptor (AR) gene can be used to predict viral respiratory infectionsymptom severity. In yet another embodiment, a genetic variation in theandrogen receptor (AR) gene can be used to predict if a patient withviral respiratory infection will need a ventilator or a respirator.

In certain embodiments, a genetic variation in the androgen receptor(AR) gene can be used to predict COVID-19 mortality. In anotherembodiment, a genetic variation in the androgen receptor (AR) gene canbe used to predict COVID-19 symptom severity. In yet another embodiment,a genetic variation in the androgen receptor (AR) gene can be used topredict COVID-19 patient's need for a ventilator or a respirator.

Many genetic variations in the androgen receptor (AR) gene can be usedto predict viral respiratory disease severity but may include, thenumber cytosine-adenine-guanine (CAG) repeats in the first exon of ARgene. In certain embodiments of present invention, a cut off value forthe number of CAG repeats the first exon of AR gene can be used todefine a person with androgen sensitivity. In one embodiment, thecut-off value for the number of CAG repeats the first exon of AR gene is24.

Various aspects of the technology describe detecting androgensensitivity in a subject by measuring polymorphisms in the androgenreceptor gene. Androgen Receptor (AR) genetic variation refers to DNAgenetic variations, expression of AR in specific tissue (RNA), includingmethylation analysis of AR (i.e., in the case of X-chromosomeinactivation). Androgen sensitivity may also include DNA geneticvariations in androgen response elements (ARE) of genes under theregulatory control of the AR. Examples of genes containing AREs include,but are not limited to, TMPRSS2 and ACE2. Polymorphisms in the androgenresponse elements can also be used to infer a subject has androgensensitivity.

In certain embodiments of the present invention genetic variations inthe androgen receptor (AR) gene or the promoter region of the AR can beused to predict a treatment response. In another embodiment of thepresent invention genetic variations in the androgen receptor (AR) geneor the promoter region of the AR can be used to select a dosage of atreatment drug. In certain embodiments genetic variations in theandrogen receptor (AR) gene or the promoter region of the AR are singlenucleotide polymorphisms (SNPs). In other embodiments SNPs that areassociated with AR expression or function are used.

Examples of genetic variations in the androgen receptor (AR) gene or thepromoter region of the AR, or are associated with AR expression orfunction include but are not limited to F877L/T878A, F877L, T878A,rs137852591, rs104894742, rs1057518177, rs1057521121, rs1057521122,rs1057523747, rs1064793480, rs1064793645, rs1064794065, rs1064794069,rs1064795250, rs1085307685, rs1085307962, rs12014709, rs1204038,rs1337080, rs137852562, rs137852563, rs137852564, rs137852565,rs137852566, rs137852567, rs137852568, rs137852569, rs137852570,rs137852571, rs137852572, rs137852573, rs137852574, rs137852575,rs137852576, rs137852577, rs137852578, rs137852579, rs137852580,rs137852581, rs137852582, rs137852583, rs137852584, rs137852585,rs137852586, rs137852587, rs137852588, rs137852589, rs137852590,rs137852592, rs137852593, rs137852594, rs137852595, rs137852596,rs137852597, rs137852598, rs137852599, rs137852600, rs137852601,rs1800053, rs201934623, rs2361634, rs5031002, rs5918757, rs6152,rs6624304, rs750324117, rs754201976, rs755226547, rs759327087,rs864622007, rs869320731, rs869320732, rs878853033, rs886039558,rs886041050, rs886041128, rs886041129, rs886041130, rs886041131,rs886041132, rs886041133, rs886041352, rs9332969, or rs9332971.

In certain embodiments of the present invention genetic variations inthe androgen response elements (ARE) of genes under the regulatorycontrol of the AR can be used to predict a treatment response. Inanother embodiment of the present invention genetic variations in theandrogen response elements (ARE) of genes under the regulatory controlof the AR can be used to select a dosage of a treatment drug. In certainembodiments genetic variations in the androgen response elements (ARE)of genes under the regulatory control of the AR are single nucleotidepolymorphisms (SNPs). In some embodiments of the present inventiongenetic variations in AREs in the TMPRSS2, ACE2, and furin gene areused. In other embodiments SNPs in the AREs or coding regions ofTMPRSS2, ACE2, and furin gene are used. In other embodiments SNPs thatare associated with TMPRSS2, ACE2, and furin expression or function areused.

Examples of genetic variations in the AREs, promoter region, codingregion, or that are associated with TMPRSS2 expression or functioninclude but are not limited to rs12329760, rs2070788, rs383510,rs463727, rs34624090, rs55964536, rs734056, rs4290734, rs34783969,rs11702475, rs35899679, rs35041537, rs8134378, rs2070788, rs9974589,rs7364083, and rs2070788.

Examples of genetic variations in the AREs, promoter region, codingregion, or that are associated with ACE2 expression or function includebut are not limited to rs2285666, G8790A, rs35803318, rs1978124,rs2048683, rs2074192, rs2106809, rs2285666, rs233575, rs4240157,rs4646155, rs4646156, rs4646174, rs4646176, rs4646188, rs6632677,rs714205, and rs879922.

Examples of genetic variations in the furin, promoter region, codingregion, or that are associated with furin expression or function includebut are not limited to rs17514846, rs2071410, rs4702, rs4932178, rs6226,and rs6227.

Androgen sensitivity may also include DNA genetic variations in androgenresponse elements (ARE) of genes under the regulatory control of the AR.Examples of genes containing AREs include, but are not limited to,TMPRSS2, furin and ACE2.

In yet another embodiment of the present invention, genetic variationsin the TMPRSS2, furin or ACE2 gene or the promoter region of theTMPRSS2, furin or ACE2 can be used to predict a treatment response. Inanother embodiment of the present invention genetic variations in theTMPRSS2, furin or ACE2 gene or the promoter region of the TMPRSS2, furinor ACE2 can be used to select a dosage of a treatment drug.

In certain embodiments, a genetic variation in the TMPRSS2, furin orACE2 gene can be used to predict mortality from viral respiratoryinfection. In another embodiment, a genetic variation in the TMPRSS2,furin or ACE2 gene can be used to predict viral respiratory infectionsymptom severity. In yet another embodiment, a genetic variation in theTMPRSS2, furin or ACE2 gene can be used to predict if a patient withviral respiratory infection will need a ventilator or a respirator.

In certain embodiments, a genetic variation in a genetic variation inthe TMPRSS2, furin or ACE2 gene can be used to predict COVID-19mortality. In another embodiment, a genetic variation in a geneticvariation in the TMPRSS2, furin or ACE2 gene can be used to predictCOVID-19 symptom severity. In yet another embodiment, a geneticvariation in a genetic variation in the TMPRSS2, furin or ACE2 gene canbe used to predict COVID-19 patient's need for a ventilator or arespirator.

Many genetic variations in the androgen receptor (AR) gene can be usedto predict viral respiratory disease severity but may include, thenumber of CAG repeats in the first exon of AR gene. In certainembodiments of present invention a cut off value for the number of CAGrepeats the first exon of AR gene can be used to define a person withandrogen sensitivity. In one embodiment the cut-off value for the numberof CAG repeats the first exon of AR gene is 24. In another embodiment,the number guanine-guanine-(any nucleotide) (GGN) (polyglycine) repeatsin the first exon of AR gene. In certain embodiments of presentinvention the number of GGN repeats is between 10 and 30. In anotherembodiment, the number of GGN repeats can be used to define a personwith androgen sensitivity. In one embodiment the ratio of CAG to GGNrepeats the first exon of AR gene is used to define a person withandrogen sensitivity. In some embodiments the number of CAG, GGN, or theratio of CAG/GGN is used to predict a treatment response or choose adosage of a drug or treatment regimen.

In certain embodiments, a genetic variation in the TMPRSS2, furin orACE2 gene is used as a predictor of anti-androgen treatment response forviral respiratory infection. In certain embodiments, a genetic variationin the TMPRSS2, furin or ACE2 gene is used to guide selection of theappropriate anti-androgen treatment for viral respiratory infection. Incertain embodiments, a genetic variation in the TMPRSS2, furin or ACE2gene is used as a predictor of anti-androgen treatment response forCOVID-19. In certain embodiments, a genetic variation in the TMPRSS2,furin or ACE2 gene is used to guide selection of the appropriateanti-androgen treatment for COVID-19. In certain embodiments, a geneticvariation in the TMPRSS2, furin or ACE2 gene is used to guide dosageselection of the appropriate anti-androgen treatment for COVID-19.

In certain embodiments, a genetic variation in the AR gene and eitherthe TMPRSS2, furin or ACE2 gene is used as a predictor of anti-androgentreatment response for viral respiratory infection. In certainembodiments, a genetic variation in the AR gene and either the TMPRSS2,furin or ACE2 gene is used to guide selection of the appropriateanti-androgen treatment for viral respiratory infection. In certainembodiments, a genetic variation in the AR gene and either the TMPRSS2,furin or ACE2 gene is used as a predictor of anti-androgen treatmentresponse for COVID-19. In certain embodiments, a genetic variation inthe AR gene and either the TMPRSS2, furin or ACE2 gene is used to guideselection of the appropriate anti-androgen treatment for COVID-19. Incertain embodiments, a genetic variation in the AR gene and either theTMPRSS2, furin or ACE2 gene is used to guide dosage selection of theappropriate anti-androgen treatment for COVID-19.

In certain embodiments of the present invention, a kit containing a DNAsample collection tool is envisioned. The genetic sample can be obtainedby buccal swab, saliva, blood, or tissue samples. The genetic sample canalso be obtained from a plucked hair sample. For example, a kit isdisclosed for detecting COVID-19 androgen sensitivity; the kit is anin-vitro diagnostic medical device intended to identify polymorphisms inthe androgen receptor gene. The kit includes a collection device (buccalswab) and a DNA diagnostic assay (laboratory based). DNA samples arecollected from a patient and mailed to a laboratory for processing.

In certain embodiments, the number of CAG repeats in the first exon ofthe AR gene is used as a genetic variant. In other embodiments, thevariants in the promoter region of the AR are used as a genetic variant.In another embodiment, a shorter CAG repeat (compared to normal) maypredispose patients to more severe viral respiratory infections. Inanother embodiment, a shorter CAG repeat (compared to normal) maypredispose patients to more severe infection fro COVID-19. In anotherembodiment, the length of the CAG repeat determines anti-androgen dosingfor the treatment of viral respiratory infections.

In certain embodiments, a method of treatment of COVID-19 patientinvolves administering an anti-androgen to a COVID-19 patient wherethere anti-androgen is any one or combination of: cyproterone acetate,megestrol acetate, chlormadinone acetate, spironolactone, medrogestone,oxendolone, osaterone, bifluranol acetate, finasteride, dutastride,flutamide, bicalutamide, nilutamide, topilutamide, enzalutamide,apalutamide, dienogest, drospirenone, medrogestone, nomegestrol acetate,promegestone, trimegestone, ketoconazole, abiraterone acetate,seviteronel, aminoglutethimide, epristeride, alfaestradiol,isotretinoin, saw palmetto, marijuana, cannabinoids, darolutamide,EZN-4176, AZD-3514, and AZD-5312, apatorsen, galeterone, ODM-2014,TRC-253, BMS-641988, proxalutamid, Luteinizing hormone-releasing hormone(LH-RH), follicle-stimulating hormone (FSH), triptorelin pamoate,docetaxel, diethylstilbestrol, tadalafil, silodosin, tamsulosinhydrochloride, naftopidil, solifenacin succinate, tamsulosin, tamsulosinhydrochloride, alfuzosin hydrochloride, prazosin hydrochloride,doxazosin, doxazosin mesylate, solifenacin succinate, allylestrenol,benzydamine hydrochloride, cefatrizine, chlormadinone acetate, flavoxatehydrochloride, gestonorone caproate, indoramin hydrochloride,mepartricin, oxybutynin chloride, phenoxybenzamine hydrochloride,terazosin, terazosin hydrochloride, or degarelix. As explained herein,the method of treatment can involve administration of a composition thatincludes an anti-androgen as an ingredient of the composition. Theanti-androgen can be present in percent amounts ranging from 0% to 100%.

In certain embodiments, a method of treatment of COVID-19 patientinvolves administering an agent that counters the effect of androgenssuch as sex hormone-binding globulin (SHBG) stimulators. As explainedherein, the method of treatment can involve administration of acomposition that includes said agent as an ingredient of thecomposition. The agent can be present in percent amounts ranging from 0%to 100%.

In certain embodiments, a method of treatment of COVID-19 patientinvolves administering an antigonadotropin. As explained herein, themethod of treatment can involve administration of a composition thatincludes an antigonadotropin as an ingredient of the composition. Theantigonadotropin can be present in percent amounts ranging from 0% to100%. The word antigonadotropin includes Gonadotropin-releasing hormoneantagonists (GnRH antagonists). Some GnRH antagonist are: Elagolix,Cetrorelix, Relugolix, Degarelix

In certain embodiments, a method of treatment of COVID-19 patientinvolves administering a mineralocorticoid and/or a glucocorticoid(e.g., anticorticotropin) suppressing androgen production in the adrenalgland. As explained herein, the method of treatment can involveadministration of a composition that includes a mineralocorticoid and/ora glucocorticoid as an ingredient of the composition. Themineralocorticoid and/or a glucocorticoid can be present in percentamounts ranging from 0% to 100%.

In certain embodiments, a method of treatment of COVID-19 patientinvolves administering an insulin sensitizing medication (e.g.,metformin). As explained herein, the method of treatment can involveadministration of a composition that includes an insulin sensitizingmedication as an ingredient of the composition. The insulin sensitizingmedication can be present in percent amounts ranging from 0% to 100%.

In certain embodiments, a method of treatment of COVID-19 patientinvolves administering a vaccine or immunogen against androstenedionethat reduces the level of testosterone or increases estrogen. Examplesof such vaccines and immunogens can be ovandrotone albumin andandrostenedione albumin. As explained herein, the method of treatmentcan involve administration of a composition that includes said vaccineor immunogen as an ingredient of the composition. The vaccine orimmunogen can be present in percent amounts ranging from 0% to 100%.

RNA interference (RNAi) is a biological process in which RNA moleculesinhibit gene expression or translation, by neutralizing targeted mRNAmolecules. RNAi selectively knocks down target genes. RNAi can also meanother names, including co-suppression, post-transcriptional genesilencing (PTGS), siRNA, quelling, or gene knock-down. In one embodimentof the present invention RNAi is used to knock down the AR. In oneembodiment of the present invention RNAi is used to knock down the AR intype II pneumocytes. In one embodiment of the present invention RNAi isused to knock down the TMPRSS2. In one embodiment of the presentinvention RNAi is used to knock down the TMPRSS2 in type II pneumocytes.In another embodiment, RNAi is used to knock down ACE2. In oneembodiment the RNAI treatment is inhaled in another embodiment the RNAitreatment is administered (e.g., via injection). In one embodiment theRNAI treatment is used to treat upper respiratory disease or any viralinfection disclosed herein (e.g., coronavirus, influenza, influenza A,influenza B, SARS-CoV-1, SARS-CoV-2, MERS-CoV and rhinoviruses). In oneembodiment, a small-interfering RNA (siRNA) directed against androgenreceptor (AR) is administered. In one embodiment, a small-interferingRNA (siRNA) directed against TMPRSS2 is administered. In one embodiment,a small-interfering RNA (siRNA) directed against ACE2 is administered.Upon administration of anti-AR siRNA, for example, SXL01, the siRNAsbind to AR mRNAs, which may result in the inhibition of translation ofthe AR protein and by preventing AR expression, AR-mediated signaling isdecreased, which leads to inhibition of TMPRSS2 or ACE2. In oneembodiment, anti-AR siRNA, for example, SXL01, is administered (e.g.,inhaled) to treat any viral infection disclosed herein (e.g.,coronavirus, influenza, influenza A, influenza B, SARS-CoV-1,SARS-CoV-2, MERS-CoV and rhinoviruses). In one embodiment, anti-ARsiRNA, for example, SXL01, is inhaled to treat SARS-CoV-2.

In certain embodiments, use of an anti-androgen for treatment can mean atreatment that promotes the production of estrogen. In anotherembodiment use of estrogen is the treatment. Examples of drugs thatpromote the production of estrogen include, but are not limited to,estrogen, estradiol, Premarin (conjugated estrogens),medroxyprogesterone acetate, Provera, medroxyprogesterone, Vivelle-Dot(estradiol patch).

In certain embodiments, use of degarelix can be used as the treatmentand/or prophylactic. For instance, degarelix can be administered for apredetermined period of time (e.g., 1 week, 2, weeks, 1 month, 2 months,etc.). The administration of degarelix can be in single or multipledoses per day over the predetermined time period. For instance, theadministration of degarelix can involve a 240 mg dose comprising a firstinjection of 120 mg and a second injection of 120 mg every 24 hours.This first and second injection routine can be administered for 1 month.The administration of degarelix can be for treatment and/or prophylacticuse before, during, and/or after a patient is first diagnosed with theviral respiratory infection and/or before, during, and/or after apatient is hospitalized due to the viral respiratory infection.

In certain embodiments, an anti-androgen is used as a prophylactictreatment for viral respiratory infection.

In certain embodiments, an anti-androgen is prescribed to a patientbelieved to be infected with COVID-19 as a prophylactic for viralrespiratory infection, i.e. severe COVID disease. In another embodimentan anti-androgen is prescribed to a patient to prevent COVID diseasesymptoms from developing. In certain embodiments, apalutamide isprescribed to patients who are diagnosed with COVID-19 infection buthave yet to demonstrate symptoms. It is specifically envisioned thathospitalization rates of populations given an anti-androgen or a placeboat early diagnosis COVID-19 can be used as a clinical endpoint fordetermining the efficacy of an anti-androgen for preventing theprogression of COVID-19 disease. It is specifically envisioned thathospitalization rates of populations given apalutamide or a placebo atearly diagnosis COVID-19 can be used as a clinical endpoint fordetermining the efficacy of apalutamide for preventing the progressionof COVID-19 disease.

In certain embodiments, dutasteride(Bis(trifluoromethyl)phenyl]-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide)is used as treatment for COVID-19. In certain embodiments, dutasteridecan be administered orally. In certain embodiments, the dutasteride isused as a prophylactic treatment for COVID-19. The treatment can involveadministration of dutasteride ranging from 0.1 mg/day to 1.0 mg/day. Thetreatment can involve administration of dutasteride before being exposedto the viral respiratory infection. This can include administration ofdutasteride at any time before being exposed to the viral respiratoryinfection up to and including 30 days prior to being exposed.

In certain embodiments, a genetic variation in the AR gene is used as apredictor of anti-androgen treatment response for viral respiratoryinfection. In certain embodiments, a genetic variation in the AR gene isused to guide selection of the appropriate anti-androgen treatment forviral respiratory infection. In certain embodiments, a genetic variationin the AR gene is used as a predictor of anti-androgen treatmentresponse for COVID-19. In certain embodiments, a genetic variation inthe AR gene is used to guide selection of the appropriate anti-androgentreatment for COVID-19. In certain embodiments, a genetic variation inthe AR gene is used to guide dosage selection of the appropriateanti-androgen treatment for COVID-19.

In one embodiment of the present invention, a composition including ananti-androgen is used to treat patients with any one or combination ofbenign prostatic hyperplasia (BPH), prostate cancer,castration-resistant prostate cancer, metastatic castration-sensitiveprostate cancer, or non-metastatic castration-resistant prostate cancer.In some embodiments, the composition including an anti-androgen can beused to treat patients with any viral infection disclosed herein (e.g.,coronavirus, influenza, influenza A, influenza B, SARS-CoV-1,SARS-CoV-2, MERS-CoV and rhinoviruses) and/or any one or combination ofbenign prostatic hyperplasia (BPH), prostate cancer,castration-resistant prostate cancer, metastatic castration-sensitiveprostate cancer, or non-metastatic castration-resistant prostate cancer.

Any of the compositions disclosed herein can include other ingredients(e.g., carrier agents) to facilitate use or administration of thecomposition via injection, oral administration, nasal administration,topological administration, etc. For instance, a composition can includea carrier or delivery vehicle optimized for delivery of the compositionto the lung. As another example, a composition can be formulated to bereleased using several different formulations or release methodsincluding time release, creams, ointments, sprays, capsules, or otherrelease methods. Capsules or vehicles that encapsulate the compositioncan include, but are not limited to, liposomes, non-ionic liposomes,niosomes, novasome I, erythromycin-Zn complex, microspheres,nanoparticles, solid lipid nanoparticles, and nanoemulsions. In someembodiments, this can include a gel or foam.

In certain embodiments, the uses (e.g., treatment, therapy, prophylactictreatment, prevention, diagnosis, prediction, selection of a drug,selection of a dosage, etc.) of the composition(s) disclosed herein canbe administered by inhalation, oral, nasal, injection, topologicalapplication, ocular application, etc. In certain embodiments, the usesof the composition can involve being administered by nebulization orvaping. In certain embodiments, the uses can involve being administeredsystemically in oral, intravenous injection, subcutaneous injection. Incertain embodiments, the uses can involve being administered topically.

In one embodiment of the present invention a therapy involving the useof a composition is delivered as a topical ocular solution, i.e., eyedrop, spray, solution, lotion, gel, ointment.

In another embodiment of the present invention, a topically appliedocular anti-androgen solution, is used as a prophylactic treatmentagainst any viral infection disclosed herein (e.g., coronavirus,influenza, influenza A, influenza B, SARS-CoV-1, SARS-CoV-2, MERS-CoVand rhinoviruses).

In another embodiment of the present invention, a topically appliedocular anti-androgen solution, is used as a prophylactic treatmentagainst any viral infection disclosed herein (e.g., coronavirus,influenza, influenza A, influenza B, SARS-CoV-1, SARS-CoV-2, MERS-CoVand rhinoviruses). The anti-androgen can be applied every 1 hr, 2 hrs, 4hrs, 8 hrs, 12 hrs, once per day, twice daily, three times a day orevery other day.

In another embodiment of the present invention, a topically appliedocular anti-androgen solution, is used as a treatment against any viralinfection disclosed herein (e.g., coronavirus, influenza, influenza A,influenza B, SARS-CoV-1, SARS-CoV-2, MERS-CoV and rhinoviruses).

In another embodiment of the present invention, a topically appliedocular anti-androgen solution, is used as a treatment against any viralinfection disclosed herein (e.g., coronavirus, influenza, influenza A,influenza B, SARS-CoV-1, SARS-CoV-2, MERS-CoV and rhinoviruses) andbenign prostatic hyperplasia and/or androgenetic alopecia.

In another embodiment of the present invention, a topically appliedocular anti-androgen solution, is used as a treatment against any viralinfection disclosed herein (e.g., coronavirus, influenza, influenza A,influenza B, SARS-CoV-1, SARS-CoV-2, MERS-CoV and rhinoviruses) andhirsutism.

In another embodiment of the present invention, a topically appliedocular anti-androgen solution, is used as a treatment against any viralinfection disclosed herein (e.g., coronavirus, influenza, influenza A,influenza B, SARS-CoV-1, SARS-CoV-2, MERS-CoV and rhinoviruses) andpolycystic ovary syndrome.

It should be noted that any of the ingredients disclosed herein can beused in combination with other any one or combination of otheringredients (e.g., an anti-androgen can be used with an agent thatcounters the effect of androgens, an antigonadotropin can be used with amineralocorticoid, an insulin sensitizing medication can be used with ananti-androgen and a mineralocorticoid, etc.). Thus, it should beunderstood that a reference to a composition can (to the extent it isnot impossible to do so) include a single composition, a combination ofcompositions, and/or a combination of a composition with anotheringredient.

It should also be understood that a reference to a use of a compositioncan (to the extent it is not impossible to do so) involve use of any oneor combination of uses (e.g., treatment, therapy, prophylactictreatment, prevention, diagnosis, prediction, selection of a drug,selection of a dosage, etc.).

It should also be understood that a reference to an administration of acomposition can (to the extent it is not impossible to do so) involveany one or combination of administrations (e.g., inhalation, oral,nasal, injection, topological application, ocular application, etc.).

In some embodiments, provided herein is an anti-androgen formulated witha carrier or delivery vehicle optimized for delivery of theanti-androgen treatment to the lung. An anti-androgen can be releasedusing several different formulations or release methods including timerelease, creams, ointments, sprays, capsules, or other release methods.Capsules or vehicles that encapsulate the anti-androgen can include, butare not limited to, liposomes, non-ionic liposomes, niosomes, novasomeI, erythromycin-Zn complex, microspheres, nanoparticles, solid lipidnanoparticles, and nanoemulsions. In some embodiments, this can includea gel or foam.

In some embodiments, the anti-androgen is combined with ananti-inflammatory agent, such as an NSAID.

In some embodiments, the anti-androgen is combined with ananti-bacterial agent, such as an azithromycin.

In some embodiments, the anti-androgen is combined with aspartame.

In some embodiments, the anti-androgen treatment is administered orally.

In other embodiments, the anti-androgen treatment is administerednasally.

In other embodiments, the anti-androgen treatment is administered byinhalation.

In other embodiments, the anti-androgen treatment is administeredtopically via the skin.

In other embodiments, the anti-androgen treatment is administeredintramuscularly or intravenously.

Any of the aforementioned anti-androgens can be used routinely, e.g.,once daily, twice daily, every other day, once a week.

As noted herein, any of the compositions disclosed herein can be used asa treatment for a viral respiratory infection and/or a prophylactic fora viral respiratory infection. The viral respiratory infection caninclude any one or combination of coronavirus, influenza, influenza A,influenza B, SARS-CoV-1, SARS-CoV-2, MERS-CoV and rhinoviruses. Any ofthe compositions can be used as a treatment and/or a prophylacticbefore, during, and/or after a patient is first diagnosed with the viralrespiratory infection and/or before, during, and/or after a patient ishospitalized due to the viral respiratory infection.

As described herein, efficacy of treatment to treat or prevent viralrespiratory infection can be categorized via patient conditions relatedto: being discharged from the hospital, being hospitalized, beingadmitted to and intensive care unit (ICU), or dying as a result of theviral respiratory infection. Efficacy may also be determined by thehospitalization rates of populations given an anti-androgen or a placeboat early diagnosis of COVID-19.

The various methods and techniques described herein provide a number ofways to carry out the invention. Of course, it is to be understood thatnot necessarily all objectives or advantages described can be achievedin accordance with any particular embodiment described herein. Thus, forexample, those skilled in the art will recognize that the methods can beperformed in a manner that achieves or optimizes one advantage or groupof advantages as taught herein without necessarily achieving otherobjectives or advantages as taught or suggested herein. A variety ofalternatives are mentioned herein. It is to be understood that someembodiments specifically include one, another, or several features,while others specifically exclude one, another, or several features,while still others mitigate a particular feature by inclusion of one,another, or several advantageous features.

Furthermore, the skilled artisan will recognize the applicability ofvarious features from different embodiments. Similarly, the variouselements, features and steps discussed herein, as well as other knownequivalents for each such element, feature or step, can be employed invarious combinations by one of ordinary skill in this art to performmethods in accordance with the principles described herein. Among thevarious elements, features, and steps some will be specifically includedand others specifically excluded in diverse embodiments.

Although the application has been disclosed in the context of certainembodiments and examples, it will be understood by those skilled in theart that the embodiments of the application extend beyond thespecifically disclosed embodiments to other alternative embodimentsand/or uses and modifications and equivalents thereof.

The recitation of ranges of values herein is merely intended to serve asa shorthand method of referring individually to each separate valuefalling within the range (the range including the end points of therange). Unless otherwise indicated herein, each individual value isincorporated into the specification as if it were individually recitedherein. All methods described herein can be performed in any suitableorder unless otherwise indicated herein or otherwise clearlycontradicted by context. The use of any and all examples, or exemplarylanguage (for example, “such as”) provided with respect to certainembodiments herein is intended merely to better illuminate theapplication and does not pose a limitation on the scope of theapplication otherwise claimed. No language in the specification shouldbe construed as indicating any non-claimed element essential to thepractice of the application.

Certain embodiments of this application are described herein. Variationson those embodiments will become apparent to those of ordinary skill inthe art upon reading the foregoing description. It is contemplated thatskilled artisans can employ such variations as appropriate, and theapplication can be practiced otherwise than specifically describedherein. Accordingly, many embodiments of this application include allmodifications and equivalents of the subject matter recited in theclaims appended hereto as permitted by applicable law. Moreover, anycombination of the herein-described elements in all possible variationsthereof is encompassed by the application unless otherwise indicatedherein or otherwise clearly contradicted by context.

All patents, patent applications, publications of patent applications,and other material, such as articles, books, specifications,publications, documents, things, and/or the like, referenced herein arehereby incorporated herein by this reference in their entirety for allpurposes, excepting any prosecution file history associated with same,any of same that is inconsistent with or in conflict with the presentdocument, or any of same that can have a limiting affect as to thebroadest scope of the claims now or later associated with the presentdocument. By way of example, should there be any inconsistency orconflict between the description, definition, and/or the use of a termassociated with any of the incorporated material and that associatedwith the present document, the description, definition, and/or the useof the term in the present document shall prevail.

EXAMPLES Example 1: In-Vitro Diagnostic Test to Predict COVID-19Mortality and Disease Severity

Investigational Device

Device Name: COVID-19 Androgen Sensitivity Test (CoVAST)

Device Background:

The COVID-19 Androgen Sensitivity Test is a non-invasive In-VitroDiagnostic device that utilizes qualitative DNA genotyping. The COVID-19Androgen Sensitivity Test requires a health care professional to collecta DNA sample using an FDA cleared DNA sample collection kit. The samplecollection kit is an ORAcollectDx OCD-100A device manufactured by DNAGenotek, Inc (previously cleared under K152464). The COVID-19 AndrogenSensitivity Test is intended to be performed at a Clinical LaboratoryImprovement Amendments (CLIA) certified laboratory. The reagents used inperforming the COVID-19 Androgen Sensitivity Test are manufactured in aGMP facility. COVID-19 Androgen Sensitivity Test reports the results ofthe DNA genotyping.

Trial Conduct

The following describes how the methods and compositions disclosedherein may be implemented.

It is contemplated for a trial study to be conducted in compliance withthe protocol approved by the Institutional Review Board (IRB), andaccording to Good Clinical Practice standards. The CoVAST Test used inthis study can be manufactured according to GMP and the specimens areanalyzed at a CLIA laboratory. It is contemplated that no deviation fromthe protocol will be implemented without the prior review and approvalof the IRB except where it may be necessary to eliminate an immediatehazard to a research subject. In such case, the deviation shouldreported to the IRB as soon as possible.

Population

In an exemplary implementation, the trial study can be a multi-centerstudy. For instance, the study may be conducted in at least 2countries—Spain and the US. It is contemplated for the protocoldisclosed herein to be followed without deviation in each country. It iscontemplated for there to be a minimum of 2 separate sites and 2separate PIs (if not deviating from the protocol then there will be aminimum of 2 separate sites and 2 separate PIs). In the US, the studyshould be approved by an IRB and in the other countries by theappropriate Ethics Committees (if not deviating from the protocol thenthe study will be approved by an IRB in the US and by the appropriateEthics Committees in other countries).

The population for this study can be subjects recruited from each site(e.g., hospital) (if not deviating from the protocol then the subjectswill be recruited from each site (hospital)). Subjects can be malesrequesting a SARS-CoV-2 test following respiratory symptoms (if notdeviating from the protocol then the subjects will be males requesting aSARS-CoV-2 test following respiratory symptoms). Subjects can be males18 years and older of any ethnicity (if not deviating from the protocolthen the subjects will be males 18 years and older of any ethnicity).

Trial Objectives

The primary purpose of the study can be to determine the predictivevalue of the CoVAST Test (if not deviating from the protocol then theprimary purpose of the study will be to determine the predictive valueof the CoVAST Test). The predictive value can be calculated based on thepositive percent agreement and negative percent agreement of the CoVASTTest (if not deviating from the protocol then the predictive value willbe calculated based on the positive percent agreement and negativepercent agreement of the CoVAST Test). The results can be presented in2×2 tables (if not deviating from the protocol then the results will bepresented in 2×2 tables).

Trial Design

Primary Study Endpoints/Secondary Endpoints

Primary Outcome Measures:

Severity of Disease (discharged, hospitalization, admission to intensivecare unit [ICU], or death) [Baseline, Day 7, Day 14, Day 21, Day 28]

Study Design/Type

The study can be (or will be) a prospective cross-sectionalobservational study. The study can (or will) have 2 arms:

Arm 1: Males first tested positive for SARS-CoV-2 at the site (hospital)with CAG length <24 (based on the CoVAST Test)

Arm 2: Males first tested positive for SARS-CoV-2 at the site (hospital)with CAG length >=24 (based on the CoVAST Test)

Study Environment:

This can be (or will be) a multi-center study to be conducted in atleast 2 countries—Spain and the US. Again, it is contemplated for thefollowing protocol to be followed without deviation. The protocol can(or will) be followed in each country. There can (or will) be a minimumof 2 separate sites and 2 separate PIs. In the US, the study can (orwill) be approved by an IRB and in the other countries by theappropriate Ethics Committees.

The study can (or will) be conducted at the site(s) listed herein i.e.,the PI's hospital. All data collection including sample collection can(or will) be performed at the site.

Study Design:

Study Phase Ia: Screening (First Site Visit)

The PI can (or will) screen each potential subject for the inclusion andexclusion criteria.

Study Phase Ib: Enrollment (First Site Visit)

Each qualified subject can (or will) complete and sign the informedconsent form.

Each subject can (or will) be assigned a subject study number.

Study Phase Ic: Sample Collection (First Site Visit)

For each subject, the PI can (or will) collect the saliva DNA sampleusing the CoVAST Test Sample Collection Kit. The sample collection can(or will) be performed in accordance with IFU for the collection kit.

The sample collection kit can (or will) be sent to the hospitallaboratory.

All information can (or will) be recorded in the appropriate CRFs.

Study Phase Id: Hospital Laboratory (First Site Visit)

The hospital laboratory can (or will) extract the DNA from the samplecollection kit utilizing the DNA extraction kit provided with the CoVASTTest kit.

The laboratory can (or will) ship the extracted DNA to the CLIAlaboratory.

Study Phase II: Primary Outcome (Days: 0, 7, 14, 21, 28):

-   -   1. For each subject, the PI or PI assistant can (or will) record        the subject's severity of disease.    -   2. All information can (or will) be recorded in the appropriate        CRF.

Inclusion Criteria

-   -   1. Male over the age of 18    -   2. First time present at the site    -   3. Laboratory confirmed SARS-CoV-2 infection    -   4. Able to give informed consent

Exclusion Criteria

-   -   1. Unable to give informed consent    -   2. Diagnosed with an additional respiratory co-infection    -   3. XXY male

Assessment of Efficacy

Efficacy Parameters

Severity of Disease

Clinical assessment of disease severity can (or will) be made byattending physician and reported to the PI or PI assistant. Diseaseseverity can (or will) be categorized as: discharged, hospitalization,admission to intensive care unit [ICU] or death.

Method and Timing

All assessments can (or will) be recorded on paper forms (CRFs) andstored with each subject's clinical study record.

The timing to complete the assessment of efficacy can (or will) be atBaseline, Day 7, Day 14, Day 21 and Day 28. After baseline assessment,the additional assessment can be performed by computerized hospitalrecord search by the PI or PI assistant.

Primary Outcome Measures:

1. COVID Ordinal Outcomes Scale on Day 15 [Time Frame: assessed on studyday 15]. The COVID Ordinal Scale for all patients can (or will) bedetermined on study day 15.

COVID Ordinal Scale can (or will) be defined as:

-   -   a. Death    -   b. Hospitalized on invasive mechanical ventilation or ECMO        (extracorporeal membrane oxygenation)    -   c. Hospitalized on non-invasive ventilation or high flow nasal        cannula    -   d. Hospitalized on supplemental oxygen    -   e. Hospitalized not on supplemental oxygen    -   f. Not hospitalized with limitation in activity (continued        symptoms)    -   g. Not hospitalized without limitation in activity (no symptoms)

Secondary Outcome Measures:

1. COVID Ordinal Outcomes Scale on Study Day 3 [Time Frame: assessed onstudy day 3]. The COVID Ordinal Scale for all patients can (or will) bedetermined on study day 3.

2. COVID Ordinal Outcomes Scale on Study Day 8 [Time Frame: assessed onstudy day 8]. COVID Ordinal Scale can (or will) be determined on studyday 8.

3. Hospital-free days to Day 28 [Time Frame: 28 days]. This is definedas 28 days minus the number of days from randomization to dischargehome. If a patient has not been discharged home prior to day 28 or diesprior to day 28, hospital free days will be zero.

Example 2: A double-blinded placebo controlled study was conducted on 97male and female health care workers working at two hospital emergencyroom departments.

At baseline, all subjects were tested negative for SARS-CoV-2 infection.50 subjects were given a daily dose of 10 mg/Kg/day oral cannabidiol.The reminder 47 subjects were given a placebo oral pill. At day 28 allsubjects were tested for SARS-CoV-2 infection. Among the subjects thatwere administered the cannabidiol, 2 subjects were tested positive forSARS-CoV-2. Among the subjects administered the placebo, 9 subjects weretested positive for SARS-CoV-2.

Example 3: A double-blinded placebo controlled study was conducted on 28male health care workers working at two hospital emergency roomdepartments.

At baseline, all subjects were tested and found to be negative forSARS-CoV-2 infection. 18 subjects were given a daily dose of 750 mg/dayoral flutamide. The reminder 10 subjects were given a placebo oral pill.At day 28 all subjects were tested again for SARS-CoV-2 infection. Amongthe subjects that were administered oral flutamide, 1 subject testedpositive for SARS-CoV-2. Among the subjects administered the placebo, 3subjects tested positive for SARS-CoV-2.

Example 4: A double-blinded placebo controlled study was conducted on 30hospitalized male patients with average age of 61 years old.

All subjects were tested and found to be positive for SARS-CoV-2infection. 15 subjects were assigned to enzalutamide treatment 160 mgqd. The other 15 subjects received standard treatment. Following 15 daysof treatment, 20% of the subjects in the enzalutamide survived while 7%of the control group survived.

Example 5: A double-blinded placebo controlled study was conducted on121 male health care workers working at two hospital emergency roomdepartments.

At baseline, all subjects were tested and found to be negative forSARS-CoV-2 infection. 68 subjects were given a daily dose of 0.25 mg/dayof oral dutasteride(Bis(trifluoromethyl)phenyl]-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide).The reminder 53 subjects were given a placebo oral pill. At day 28 allsubjects were tested again for SARS-CoV-2 infection. Among the subjectsthat were administered oral dutasteride, 3 (4.4%) subject testedpositive for SARS-CoV-2. Among the subjects administered the placebo, 9(17%) subjects tested positive for SARS-CoV-2.

Example 6: A double-blinded placebo controlled study was conducted on400 male patients with average age of 43.2 years old.

Patients were diagnosed with SARS-CoV-2 infection but were showingrelatively mild symptoms. Patients were prescribed apalutamide 60 mg ora placebo and instructed to take 4 tablets daily. Patients wereinstructed to go home but return to the hospital if symptoms becameworse. Efficacy parameters were defined as 1.) COVID-19 Diagnosis:COVID-19 positive diagnosis is defined as subject exhibiting symptoms ofacute respiratory infection, defined as one or more of the followingcough, fever (>37.5° C./99.5° F.), shortness of breath, sore throat, anda positive SARS-CoV-2 rtPCR test 2.) COVID-19 Hospitalization defined asconfirmed hospitalization due to COVID-19, and 3.) Symptoms Severity ofCOVID-19 defined as symptoms severity of COVID-19 using Brescia-COVIDRespiratory Severity Scale (BCRSS).

All subjects were tested and found to be positive for SARS-CoV-2infection. All subjects were monitored for one month after theinitiation of the therapy. 13 of 200 subjects in the apalutamide (240mg) arm were admitted to the hospital after their first visit. Theaverage BCRSS score for the 13 admitted patients was 3.2. 49 of 200 inthe placebo group were admitted to the hospital with an average BCRSSscore of 5.4.

Example 7: A double-blinded placebo controlled study was conducted on113 hospitalized male patients with average age of 57 years old.

All subjects were tested and found to be positive for SARS-CoV-2infection. 60 subjects were given an injection of cyproterone acetate(300 mg). The other 53 subjects received standard treatment. Following15 days of treatment, 84% of the subjects in the cyproterone acetatesurvived while 64% of the control group survived.

Example 8: A double-blinded placebo controlled study was conducted on340 male patients with average age of 39.2 years old.

Patients were diagnosed with SARS-CoV-2 infection but were showingrelatively mild symptoms. Patients were divided into one of two arms.The treatment arm received a subcutaneous injection of degarelix (120mg) at the start of the trial. Each group received tablets ofbicalutamide (50 mg) or a placebo and were instructed to take 1 tabletdaily. Patients were instructed to go home but return to the hospital ifsymptoms became worse. Efficacy parameters were defined as 1.) COVID-19Diagnosis: COVID-19 positive diagnosis is defined as subject exhibitingsymptoms of acute respiratory infection, defined as one or more of thefollowing cough, fever (>37.5° C./99.5° F.), shortness of breath, sorethroat, and a positive SARS-CoV-2 rtPCR test 2.) COVID-19Hospitalization defined as confirmed hospitalization due to COVID-19,and 3.) Symptoms Severity of COVID-19 defined as symptoms severity ofCOVID-19 using Brescia-COVID Respiratory Severity Scale (BCRSS).

All subjects were tested and found to be positive for SARS-CoV-2infection. All subjects were monitored for one month after theinitiation of the therapy. 2 of 180 subjects in the bicalutamide plusdegarelix arm were admitted to the hospital after their first visit. Theaverage BCRSS score for the 2 admitted patients was 2.5. 31 of 160 inthe placebo group were admitted to the hospital with an average BCRSSscore of 6.2.

Example 9: A controlled study was conducted on 140 male patients withaverage age of 42.6 years old. Patients were diagnosed with SARS-CoV-2infection but were showing relatively mild symptoms. Patients weredivided into one of two arms. The treatment arm received a subcutaneousinjection of degarelix (120 mg) at the start of the trial, the controlarm received standard care. Patients were instructed to go home butreturn to the hospital if symptoms became worse. Efficacy parameterswere defined as 1.) COVID-19 Diagnosis: COVID-19 positive diagnosis isdefined as subject exhibiting symptoms of acute respiratory infection,defined as one or more of the following cough, fever (>37.5° C./99.5°F.), shortness of breath, sore throat, and a positive SARS-CoV-2 rtPCRtest 2.) COVID-19 Hospitalization defined as confirmed hospitalizationdue to COVID-19, and 3.) Symptoms Severity of COVID-19 defined assymptoms severity of COVID-19 using Brescia-COVID Respiratory SeverityScale (BCRSS).

All subjects were tested and found to be positive for SARS-CoV-2infection. All subjects were monitored for one month after theinitiation of the therapy. 3 of 80 subjects in the degarelix arm wereadmitted to the hospital after their first visit. The average BCRSSscore for the 2 admitted patients was 1.3. 12 of 60 subjects in thestandard care group were admitted to the hospital with an average BCRSSscore of 4.6.

Example 10: A double-blinded placebo controlled study was conducted on25 male patients admitted to the hospital for complication resultingfrom flu with average age of 68.4 years old. Patients were diagnosedwith Influenza A infection. Patients were divided into one of two arms.The treatment arm received a subcutaneous injection of degarelix (120mg) at the start of the trial. Each group received 1 tablet ofbicalutamide (50 mg) or a placebo daily. Patient progress was monitoredby primary care physician. Efficacy parameters were defined as 1.) timeto alleviation of fever 2.) mortality and length of hospital stay 3.)change in virus titer 48 hours after hospital admission.

All subjects were tested and found to be positive for Influenza Ainfection. 15 subjects were in the treatment group and 9 were in theplacebo arm. Overall, the time to alleviation of fever was lower in thetreated group compared with the control group [mean difference (MD),−7.17 hours; 95% confidence interval (CI) −11.00 to −3.34]. Mortality,length of hospital stay, change in virus titer 48 hours after admission,and the incidence of adverse events in these patients were notsignificantly different between the two groups.

Example 11: A double-blinded placebo controlled study was conducted on36 male health care workers working at two hospital emergency roomdepartments.

At baseline, all subjects were tested and found to be negative forSARS-CoV-2 infection. 18 subjects applied twice daily a topical ocularsolution containing a low dosage finasteride. The reminder 18 subjectswere given a placebo vehicle ocular solution. At day 28 all subjectswere tested again for SARS-CoV-2 infection. Among the subjects that wereadministered finasteride, 1 subject tested positive for SARS-CoV-2.Among the subjects administered the placebo, 6 subjects tested positivefor SARS-CoV-2.

Example 12: In-vitro Diagnostic Test to Guide Androgen DeprivationTherapy Dosage for COVID-19 Patients Investigational Device

Device Name: COVID-19 Androgen Deprivation Therapy Dosage Selector(CoADTS)

Device Background:

COVID-19 Androgen Deprivation Therapy Dosage Selector (CoADTS) is anon-invasive In-Vitro Diagnostic device that utilizes qualitative DNAgenotyping. CoADTS test requires a health care professional to collect aDNA sample using an FDA cleared DNA sample collection kit. The samplecollection kit is an ORAcollectDx OCD-100A device manufactured by DNAGenotek, Inc (previously cleared under K152464). CoADTS test is intendedto be performed at a Clinical Laboratory Improvement Amendments (CLIA)certified laboratory. The reagents used in performing the CoADTS testare manufactured in a GMP facility. CoADTS test reports the results ofthe DNA genotyping.

Trial Conduct

This study will be conducted in compliance with the protocol approved bythe Institutional Review Board, and according to Good Clinical Practicestandards. The CoADTS Test used in this study is manufactured accordingto GMP and the specimens will be analyzed at a CLIA laboratory. Nodeviation from the protocol will be implemented without the prior reviewand approval of the IRB except where it may be necessary to eliminate animmediate hazard to a research subject. In such case, the deviation willbe reported to the IRB as soon as possible.

Population

This is a multi-center study to be conducted in at least 2countries—Spain and the US. This exact protocol will be followed in eachcountry. There will be a minimum of 2 separate sites and 2 separate PIs.In the US, the study will be approved by an IRB and in the othercountries by the appropriate Ethics Committees.

The population for this study will be subjects recruited from each site(hospital).

Subjects will be males requesting a SARS-CoV-2 test followingrespiratory symptoms.

Subjects will be males 18 years and older of any ethnicity.

Trial Objectives

The primary purpose of this study is to determine the predictive valueof the CoADTS Test. The predictive value will be calculated based on thepositive percent agreement and negative percent agreement of the CoADTSTest. The results will be presented in 2×2 tables.

Trial Design

Primary Study Endpoints/Secondary Endpoints

Primary Outcome Measures:

Severity of Disease (discharged, hospitalization, admission to intensivecare unit [ICU], and death) [Baseline, Day 7, Day 14, Day 21, Day 28]

Study Design/Type

This study is a prospective cross-sectional observational study. Thestudy will have 4 arms:

Arm 1: Males first tested positive for SARS-CoV-2 at the site (hospital)with CAG length <24 (based on the CoADTS Test) and TMPRSS2 SNP(r58134378) positive (G)

Arm 2: Males first tested positive for SARS-CoV-2 at the site (hospital)with CAG length >=24 (based on the CoADTS Test) and TMPRSS2 SNP(r58134378) positive (G)

Arm 3: Males first tested positive for SARS-CoV-2 at the site (hospital)with CAG length <24 (based on the CoADTS Test) and TMPRSS2 SNP(r58134378) negative (A)

Arm 4: Males first tested positive for SARS-CoV-2 at the site (hospital)with CAG length >=24 (based on the CoADTS Test) and TMPRSS2 SNP(r58134378) negative (A)

Study Environment:

This is a multi-center study to be conducted in at least 2countries—Spain and the US. This exact protocol will be followed in eachcountry. There will be a minimum of 2 separate sites and 2 separate PIs.In the US, the study will be approved by an IRB and in the othercountries by the appropriate Ethics Committees.

The study will be conducted at the site(s) listed above i.e., the PI'shospital. All data collection including sample collection will beperformed at the site.

Study Design:

Study Phase Ia: Screening (First Site Visit)

The PI will screen each potential subject for the inclusion andexclusion criteria.

Study Phase Ib: Enrollment (First Site Visit)

Each qualified subject will complete and sign the informed consent form

Each subject will be assigned a subject study number

Study Phase Ic: Sample Collection (First Site Visit)

For each subject, the PI will collect the saliva DNA sample using theCoADTS Test Sample Collection Kit. The sample collection will beperformed in accordance with IFU for the collection kit.

The sample collection kit will be sent to the hospital laboratory.

All information will be recorded in the appropriate CRFs.

Study Phase Id: Hospital Laboratory (First Site Visit)

The hospital laboratory will extract the DNA from the sample collectionkit utilizing the DNA extraction kit provided with the CoADTS Test kit.

The laboratory will ship the extracted DNA to the CLIA laboratory

Study Phase II: Primary Outcome (Days: 0, 7, 14, 21, 28):

-   -   1. For each subject, the PI or PI assistant will record the        subject's severity of disease    -   2. All information will be recorded in the appropriate CRFs        Inclusion Criteria

Male over the age of 18

First time present at the site

Laboratory confirmed SARS-CoV-2 infection

Able to give informed consent Exclusion Criteria

Unable to give informed consent

Diagnosed with an additional respiratory co-infection

XXY males

Assessment of Efficacy

Efficacy Parameters

Severity of Disease

Clinical assessment of disease severity will be made by attendingphysician and reported to the PI or PI assistant. Disease severity willbe categorized as: discharged, hospitalization, admission to intensivecare unit [ICU] or and death.

Method and Timing

All assessments described in section 5.1 will be recorded on paper forms(CRFs) and stored with each subject's clinical study record.

The timing to complete the assessment of efficacy will be at Baseline,Day 7, Day 14, Day 21 and Day 28. After baseline assessment, theadditional assessment can be performed by computerized hospital recordsearch by the PI or PI assistant.

Example 13: A controlled study was conducted on 100 male patients withaverage age of 48.3 years old. Patients were diagnosed with SARS-CoV-2infection but were showing relatively mild symptoms. Patients weredivided into one of two arms. The treatment arm was prescribedbicalutamide (50 mg) once daily at the start of the trial, the controlarm received standard care. Patients were instructed to go home butreturn to the hospital if symptoms became worse. Efficacy parameterswere defined as 1.) COVID-19 Diagnosis: COVID-19 positive diagnosis weredefined as subject exhibiting symptoms of acute respiratory infection,defined as one or more of the following cough, fever (>37.5° C./99.5°F.), shortness of breath, sore throat, and a positive SARS-CoV-2 rtPCRtest 2.) COVID-19 Hospitalization was defined as confirmedhospitalization due to COVID-19, and 3.) Symptoms Severity of COVID-19was defined as symptoms severity of COVID-19 using Brescia-COVIDRespiratory Severity Scale (BCRSS).

All subjects were tested and found to be positive for SARS-CoV-2infection. All subjects were monitored for one month after theinitiation of the therapy. 6 of 50 subjects in the bicalutamide arm wereadmitted to the hospital after their first visit. The average BCRSSscore for the 6 admitted patients was 1.9. 17 of 50 subjects in thestandard care group were admitted to the hospital with an average BCRSSscore of 4.1.

Example 14: A controlled study was conducted on 40 male patients withaverage age of 41.6 years old. Patients were diagnosed with SARS-CoV-2infection but were showing relatively mild symptoms. Patients weredivided into one of two arms. The treatment arm was prescribeddarolutamide (300 mg) orally twice daily at the start of the trial, thecontrol arm received standard care. Patients were instructed to go homebut return to the hospital if symptoms became worse. Efficacy parameterswere defined as 1.) COVID-19 Diagnosis: COVID-19 positive diagnosis wasdefined as subject exhibiting symptoms of acute respiratory infection,defined as one or more of the following cough, fever (>37.5° C./99.5°F.), shortness of breath, sore throat, and a positive SARS-CoV-2 rtPCRtest 2.) COVID-19 Hospitalization was defined as confirmedhospitalization due to COVID-19, and 3.) Symptoms Severity of COVID-19was defined as symptoms severity of COVID-19 using Brescia-COVIDRespiratory Severity Scale (BCRSS).

All subjects were tested and found to be positive for SARS-CoV-2infection. All subjects were monitored for one month after theinitiation of the therapy. 1 of 20 subjects in the darolutamide arm wasadmitted to the hospital after their first visit. The patient's BCRSSscore was 2. 3 of 20 subjects in the standard care group were admittedto the hospital with an average BCRSS score of 3.6.

Example 15: A controlled study was conducted on 150 male patients withaverage age of 45.7 years old. Patients were diagnosed with SARS-CoV-2infection but were showing relatively mild symptoms. Patients weredivided into one of two arms. The treatment arm was prescribedabiraterone (500 mg) twice daily at the start of the trial, the controlarm received standard care. Patients were instructed to go home butreturn to the hospital if symptoms became worse. Efficacy parameterswere defined as 1.) COVID-19 Diagnosis: COVID-19 positive diagnosis wasdefined as subject exhibiting symptoms of acute respiratory infection,defined as one or more of the following cough, fever (>37.5° C./99.5°F.), shortness of breath, sore throat, and a positive SARS-CoV-2 rtPCRtest 2.) COVID-19 Hospitalization was defined as confirmedhospitalization due to COVID-19, and 3.) Symptoms Severity of COVID-19was defined as symptoms severity of COVID-19 using Brescia-COVIDRespiratory Severity Scale (BCRSS).

All subjects were tested and found to be positive for SARS-CoV-2infection. All subjects were monitored for one month after theinitiation of the therapy. 4 of 75 subjects in the abiraterone arm wereadmitted to the hospital after their first visit. The patients averageBCRSS score was 1.8. 15 of 75 subjects in the standard care group wereadmitted to the hospital with an average BCRSS score of 4.7.

Example 16: A controlled study was conducted on 90 male patients withaverage age of 51 years old. Patients were diagnosed with SARS-CoV-2infection but were showing relatively mild symptoms. Patients weredivided into one of two arms. The treatment arm was prescribednilutamide (300 mg) orally once daily at the start of the trial, thecontrol arm received standard care. Patients were instructed to go homebut return to the hospital if symptoms became worse. Efficacy parameterswere defined as 1.) COVID-19 Diagnosis: COVID-19 positive diagnosis wasdefined as subject exhibiting symptoms of acute respiratory infection,defined as one or more of the following cough, fever (>37.5° C./99.5°F.), shortness of breath, sore throat, and a positive SARS-CoV-2 rtPCRtest 2.) COVID-19 Hospitalization was defined as confirmedhospitalization due to COVID-19, and 3.) Symptoms Severity of COVID-19defined as symptoms severity of COVID-19 using Brescia-COVID RespiratorySeverity Scale (BCRSS).

All subjects were tested and found to be positive for SARS-CoV-2infection. All subjects were monitored for one month after theinitiation of the therapy. 3 of 50 subjects in the nilutamide arm wereadmitted to the hospital after their first visit. The patients BCRSSscore was 1.3. 8 of 40 subjects in the standard care group were admittedto the hospital with an average BCRSS score of 4.0.

Example 17: A controlled study was conducted on 16 male patients withaverage age of 64 years old. Patients were diagnosed with SARS-CoV-2infection but were showing relatively mild symptoms. Patients weredivided into one of two arms. The treatment arm received docetaxel 75mg/m2 IV over 1 hour at the start of the trial, the control arm receivedstandard care. Patients were instructed to go home but return to thehospital if symptoms became worse. Efficacy parameters were defined as1.) COVID-19 Diagnosis: COVID-19 positive diagnosis was defined assubject exhibiting symptoms of acute respiratory infection, defined asone or more of the following cough, fever (>37.5° C./99.5° F.),shortness of breath, sore throat, and a positive SARS-CoV-2 rtPCR test2.) COVID-19 Hospitalization defined as confirmed hospitalization due toCOVID-19, and 3.) Symptoms Severity of COVID-19 was defined as symptomsseverity of COVID-19 using Brescia-COVID Respiratory Severity Scale(BCRSS).

All subjects were tested and found to be positive for SARS-CoV-2infection. All subjects were monitored for one month after theinitiation of the therapy. 0 of 8 subjects in the docetaxel arm wereadmitted to the hospital after their first visit. 2 of 8 subjects in thestandard care group were admitted to the hospital with an average BCRSSscore of 4.5.

It should be noted that the dosage used in administering embodiments ofthe compositions can be low and still be effective. A low dosage can bewithin a range from 1/10× to 1× of the following exemplary dosageslisted:

topical skin application of finasteride at 10% (w/w)oral finasteride at 0.1-10 mgdutasteride at 0.1 mg/day to 1.0 mg/daydegarelix at 240 mgoral cannabidiol at 10/mg/Kg/dayoral flutamide at 750 mg/dayenzalutamide at 160 mg qdoral dutasteride at 0.25 mg/dayapalutamide at 60 mg 4 times per dayinjection of cyproterone acetate (300 mg).subcutaneous injection of degarelix (120 mg)bicalutamide at 50 mg per daysubcutaneous injection of degarelix (120 mg)oral darolutamide at 300 mg twice dailyabiraterone at 500 mg twice dailyoral nilutamide at 300 mg once dailydocetaxel at 75 mg/m2 IV over 1 hour

However, dosages within a range from 1/10× to 3× of the above identifieddosages can be used. Thus, dosages can be within a range from:

topical skin application of finasteride at 1-30% (w/w)oral finasteride at 0.01-30 mgdutasteride at 0.1 mg/day to 3.0 mg/daydegarelix at 24 mg-720 mgoral cannabidiol at 1-30/mg/Kg/dayoral flutamide at 75-2,250 mg/dayenzalutamide at 16-480 mg qdoral dutasteride at 0.025-0.75 mg/dayapalutamide at 6-180 mg 4 times per dayinjection of cyproterone acetate (30-900 mg).subcutaneous injection of degarelix (12-360 mg)bicalutamide at 5-150 mg per daysubcutaneous injection of degarelix (12-360 mg)oral darolutamide at 30-900 mg twice dailyabiraterone at 50-1500 mg twice dailyoral nilutamide at 30-900 mg once dailydocetaxel at 7.5-225 mg/m2 IV over 1 hour

1-7. (canceled)
 8. A method of treating a patient having or suspected ofhaving a viral respiratory infection, the method comprising:administering a composition to the patient, the composition includingany one or combination of: an androgen receptor antagonists oranti-androgen; an androgen synthesis inhibitor; an agent that countersthe effect of androgens; a globulin (SHBG) stimulator; anantigonadotropins; a mineralocorticoid to suppress androgen productionin the adrenal gland; a glucocorticoid to suppress androgen productionin the adrenal gland; an insulin sensitizing medication; and vaccine oran immunogen against androstenedione that reduces the level oftestosterone or increases estrogen.
 9. The method of claim 8, wherein:the anti-androgen is any one or combination of: cyproterone acetate,megestrol acetate, chlormadinone acetate, spironolactone, medrogestone,oxendolone, osaterone, bifluranol, finasteride, dutasteride, flutamide,bicalutamide, nilutamide, topilutamide, enzalutamide, apalutamide,dienogest, drospirenone, medrogestone, nomegestrol acetate,promegestone, trimegestone, ketoconazole, abiraterone acetate,seviteronel, aminoglutethimide, epristeride, alfaestradiol,isotretinoin, saw palmetto, darolutamide, galeterone, proxalutamide,triptorelin pamoate, allylestrenol, chlormadinone acetate or degarelix;the agent that counters the effect of androgens is a sex hormone-bindingglobulin (SHBG) stimulator; the glucocorticoid is anticorticotropin; andthe insulin sensitizing medication is metformin.
 10. The method of claim8, wherein the administration of the composition involves any one orcombination of topical application to the skin, nasal application,sub-lingual application, oral application, via injection, viainhalation, or ocular application.
 11. The method of claim 8, whereinthe viral respiratory infection is any one or combination ofcoronavirus, influenza, influenza A, influenza B, SARS-CoV-1,SARS-CoV-2, MERS-CoV or rhinoviruses.
 12. The method of claim 8, whereinthe composition is used as a treatment for the viral respiratoryinfection, a therapy for the viral respiratory infection, a prophylacticfor the viral respiratory infection, and/or a preventive measure forcontracting the viral respiratory infection.
 13. The method of claim 8,wherein the treatment involves administering the composition as atreatment for the viral respiratory infection and/or a prophylactic forthe viral respiratory infection before, during, and/or after the patientis first diagnosed with the viral respiratory infection and/or before,during, and/or after the patient is hospitalized due to the viralrespiratory infection.
 14. The method of claim 12, wherein thecomposition is further used as a treatment for prostate cancer,castration-resistant prostate cancer, metastatic castration-sensitiveprostate cancer, non-metastatic castration-resistant prostate cancerand/or benign prostatic hyperplasia.
 15. The method of claim 8, furthercomprising predicting anti-androgen treatment response via evaluation ofgenetic variation in the gene and/or promotor region of the androgenreceptor (AR).
 16. The method of claim 15, further comprising guidingselection of anti-androgen treatment and/or dosage selection of theselected anti-androgen treatment based on the predicted anti-androgentreatment response.
 17. The method of claim 15, wherein predicting theanti-androgen treatment response involves measuring polymorphisms in theAR gene.
 18. The method of claim 15, wherein: the number ofcytosine-adenine-guanine (CAG) repeats in the first exon of the AR gene,the number of guanine-guanine-(any nucleotide) (GGN) repeats in thefirst exon in the AR gene, and/or a ratio of CAG/GGN repeats is used asthe genetic variant; and a cut off value for the number of CAG repeatsthe first exon of AR gene is used to define a person with androgensensitivity.
 19. The method of claim 18, wherein the cut-off value forthe number of CAG repeats the first exon of AR gene is between 10 and30.
 20. The method of claim 15, wherein variants in the promoter regionof the AR are used as the genetic variant.
 21. The method of claim 8,wherein the anti-androgen is combined with any one or combination of ananti-inflammatory agent, an anti-bacterial agent, or aspartame.
 22. Themethod of claim 21, wherein the viral respiratory infection isSARS-CoV-2.
 23. The method of claim 8, wherein administering thecomposition involves administering: topical skin application offinasteride at 1-30% (w/w), oral finasteride at 0.01-30 mg, dutasterideat 0.1 mg/day to 3.0 mg/day, degarelix at 24 mg-720 mg, oral flutamideat 75-2,250 mg/day, enzalutamide at 16-480 mg qd, oral dutasteride at0.025-0.75 mg/day, apalutamide at 6-180 mg 4 times per day, injection of30-900 mg of cyproterone acetate, subcutaneous injection of 12-360 mg ofdegarelix, bicalutamide at 5-150 mg per day, subcutaneous injection of12-360 mg of degarelix, oral darolutamide at 30-900 mg twice daily,abiraterone at 50-1500 mg twice daily, oral nilutamide at 30-900 mg oncedaily, or docetaxel at 7.5-225 mg/m² IV over 1 hour.
 24. The method ofclaim 8, wherein administering the composition involves administering:topical skin application of finasteride at 1-10% (w/w), oral finasterideat 0.1-10 mg, dutasteride at 0.1 mg/day to 1.0 mg/day, degarelix at 24mg-240 mg, oral flutamide at 75-750 mg/day, enzalutamide at 16-160 mgqd, oral dutasteride at 0.025-0.25 mg/day, apalutamide at 6-60 mg 4times per day, injection of 30-300 mg of cyproterone acetate,subcutaneous injection of 12-120 mg of degarelix, bicalutamide at 5-50mg per day, subcutaneous injection of 12-120 mg of degarelix, oraldarolutamide at 30-300 mg twice daily, abiraterone at 50-500 mg twicedaily, oral nilutamide at 30-300 mg once daily, or docetaxel at 7.5-750mg/m² IV over 1 hour.
 25. A method of treating a patient having orsuspected of having a viral respiratory infection, the methodcomprising: determining the risk of severity or mortality of the viralrespiratory infection for the patient by identifying and measuringgenetic variation in the gene and/or promotor region of any one orcombination of the androgen receptor (AR), TMPRSS2, furin, or ACE2; andselecting a composition and a dosage for the composition based on thedetermined risk of severity or mortality; administering the compositionto the patient, the composition including any one or combination of: anandrogen receptor antagonists or anti-androgen; an androgen synthesisinhibitor; an agent that counters the effect of androgens; a globulin(SHBG) stimulator; an antigonadotropin; a mineralocorticoid to suppressandrogen production in the adrenal gland; a glucocorticoid to suppressandrogen production in the adrenal gland; an insulin sensitizingmedication; and vaccine or an immunogen against androstenedione thatreduces the level of testosterone or increases estrogen.
 26. The methodof claim 25, wherein the method involves use of a kit, wherein: agenetic sample via buccal swab, saliva sample, blood sample, tissuesample, and/or hair sample is obtained via a deoxyribonucleic acid (DNA)sample collection unit; polymorphisms in the androgen receptor gene areidentified via a viral respiratory infection sensitivity unit; and anassay analysis is performed using a DNA diagnostic assay.
 27. The methodof claim 25, further comprising: predicting anti-androgen treatmentresponse via evaluation of a genetic variation in the gene and/orpromotor region in any one or combination of AR, TMPRSS2, furin, orACE2.
 28. The method of claim 27, wherein the genetic variation includesany one or combination of: one or more of: F877L/T878A, F877L, T878A,rs137852591, rs104894742, rs1057518177, rs1057521121, rs1057521122,rs1057523747, rs1064793480, rs1064793645, rs1064794065, rs1064794069,rs1064795250, rs1085307685, rs1085307962, rs12014709, rs1204038,rs1337080, rs137852562, rs137852563, rs137852564, rs137852565,rs137852566, rs137852567, rs137852568, rs137852569, rs137852570,rs137852571, rs137852572, rs137852573, rs137852574, rs137852575,rs137852576, rs137852577, rs137852578, rs137852579, rs137852580,rs137852581, rs137852582, rs137852583, rs137852584, rs137852585,rs137852586, rs137852587, rs137852588, rs137852589, rs137852590,rs137852592, rs137852593, rs137852594, rs137852595, rs137852596,rs137852597, rs137852598, rs137852599, rs137852600, rs137852601,rs1800053, rs201934623, rs2361634, rs5031002, rs5918757, rs6152,rs6624304, rs750324117, rs754201976, rs755226547, rs759327087,rs864622007, rs869320731, rs869320732, rs878853033, rs886039558,rs886041050, rs886041128, rs886041129, rs886041130, rs886041131,rs886041132, rs886041133, rs886041352, rs9332969, or rs9332971; one ormore of: rs12329760, rs2070788, rs383510, rs463727, rs34624090,rs55964536, rs734056, rs4290734, rs34783969, rs11702475, rs35899679,rs35041537, rs8134378, rs2070788, rs9974589, rs7364083, or rs2070788;one or more of: rs2285666, G8790A, rs35803318, rs1978124, rs2048683,rs2074192, rs2106809, rs2285666, rs233575, rs4240157, rs4646155,rs4646156, rs4646174, rs4646176, rs4646188, rs6632677, rs714205, orrs879922; or one or more of: rs17514846, rs2071410, rs4702, rs4932178,rs6226, or rs6227.